Hyaluronan - a functional and structural sweet spot in the tissue microenvironment

Frontiers in Immunology

Volumn 6, Issue MAY, 2015, Pages

  Monslow, James ^a   Govindaraju, Priya ^a   Puré, Ellen ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Homeostasis; Hyaluronan; Matrix; Pathogenesis; Remodeling

Indexed keywords

BETA INTERFERON; CD36 ANTIGEN; CHEMOKINE RECEPTOR CXCR4; COLLAGENASE 3; CYCLOOXYGENASE 2; FIBROBLAST GROWTH FACTOR 2; HERMES ANTIGEN; HYALURONIC ACID; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 12; INTERLEUKIN 4; INTERSTITIAL COLLAGENASE; MONOCYTE CHEMOTACTIC PROTEIN 1; RANTES; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; TOLL LIKE RECEPTOR 4; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND;

CANCER GROWTH; CATABOLISM; ENZYME ACTIVITY; EXTRACELLULAR MATRIX; FRAGMENTATION REACTION; HOMEOSTASIS; HUMAN; INFLAMMATION; INTRACELLULAR SIGNALING; MOLECULAR WEIGHT; NONHUMAN; PATHOPHYSIOLOGY; PROTEIN EXPRESSION; REVIEW; TUMOR MICROENVIRONMENT;

EID: 84934289193     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00231     Document Type: Review

References (289)

1. Meyer K, Palmer JW. The polysaccharide of the vitreous humor. J Biol Chem (1934) 107:629-34.
2. Simpson MA, Heldin P, editors. Hyaluronan signaling and turnover. Adv Cancer Res (2014) 123:1-385.
3. Fraser JR, Laurent TC, Laurent UB. Hyaluronan: its nature, distribution, functions and turnover. J Intern Med (1997) 242:27-33. doi:10.1046/j.1365-2796.1997.00170.x
4. Jiang D, Liang J, Noble PW. Hyaluronan as an immune regulator in human diseases. Physiol Rev (2011) 91:221-64. doi:10.1152/physrev.00052.2009
5. Toole BP, Wight TN, Tammi MI. Hyaluronan-cell interactions in cancer and vascular disease. J Biol Chem (2002) 277:4593-6. doi:10.1074/jbc. R100039200
6. Misra S, Heldin P, Hascall VC, Karamanos NK, Skandalis SS, Markwald RR, et al. Hyaluronan-CD44 interactions as potential targets for cancer therapy. FEBS J (2011) 278:1429-43. doi:10.1111/j.1742-4658.2011.08071.x
7. Toole BP. Hyaluronan promotes the malignant phenotype. Glycobiology (2002) 12:37R-42R. doi:10.1093/glycob/12.3.37R
8. Aya KL, Stern R. Hyaluronan in wound healing: rediscovering a major player. Wound Repair Regen (2014) 22:579-93. doi:10.1111/wrr.12214
9. Singleton PA, Lennon FE. Acute lung injury regulation by hyaluronan. J Allergy Ther (2011) (Suppl 4):S4-003. doi:10.4172/2155-6121.S4-003
10. Ruppert SM, Hawn TR, Arrigoni A, Wight TN, Bollyky PL. Tissue integrity signals communicated by high-molecular weight hyaluronan and the resolution of inflammation. Immunol Res (2014) 58:186-92. doi:10.1007/s12026-014-8495-2
11. Wang A, de la Motte C, Lauer M, Hascall V. Hyaluronan matrices in pathobiological processes. FEBS J (2011) 278:1412-8. doi:10.1111/j.1742-4658.2011.08069.x
12. Petrey AC, de la Motte CA. Hyaluronan, a crucial regulator of inflammation. Front Immunol (2014) 5:101. doi:10.3389/fimmu.2014.00101
13. Jiang D, Liang J, Noble PW. Hyaluronan in tissue injury and repair. Annu Rev Cell Dev Biol (2007) 23:435-61. doi:10.1146/annurev.cellbio.23.090506.123337
14. Puré E, Cuff CA. A crucial role for CD44 in inflammation. Trends Mol Med (2001) 7:213-21. doi:10.1016/S1471-4914(01)01963-3
15. Orian-Rousseau V, Sleeman J. CD44 is a multidomain signaling platform that integrates extracellular matrix cues with growth factor and cytokine signals. Adv Cancer Res (2014) 123:231-54. doi:10.1016/B978-0-12-800092-2.00009-5
16. Stern R, Asari AA, Sugahara KN. Hyaluronan fragments: an information-rich system. Eur J Cell Biol (2006) 85:699-715. doi:10.1016/j.ejcb.2006.05.009
17. Singleton PA. Hyaluronan regulation of endothelial barrier function in cancer. Adv Cancer Res (2014) 123:191-209. doi:10.1016/B978-0-12-800092-2.00007-1
18. Pardue EL, Ibrahim S, Ramamurthi A. Role of hyaluronan in angiogenesis and its utility to angiogenic tissue engineering. Organogenesis (2008) 4:203-14. doi:10.4161/org.4.4.6926
19. Ghosh P, Guidolin D. Potential mechanism of action of intra-articular hyaluronan therapy in osteoarthritis: are the effects molecular weight dependent? Semin Arthritis Rheum (2002) 32:10-37. doi:10.1053/sarh.2002.33720
20. Toole BP. Hyaluronan-CD44 interactions in cancer: paradoxes and possibilities. Clin Cancer Res (2009) 15:7462-8. doi:10.1158/1078-0432.CCR-09-0479
21. Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M, Ablaeva J, et al. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature (2013) 499:346-9. doi:10.1038/nature12234
22. Puré E, Assoian RK. Rheostatic signaling by CD44 and hyaluronan. Cell Signal (2009) 21:651-5. doi:10.1016/j.cellsig.2009.01.024
23. Kultti A, Li X, Jiang P, Thompson CB, Frost GI, Shepard HM. Therapeutic targeting of hyaluronan in the tumor stroma. Cancers (Basel) (2012) 4:873-903. doi:10.3390/cancers4030873
24. Karousou E, D'Angelo ML, Kouvidi K, Vigetti D, Viola M, Nikitovic D, et al. Collagen VI and hyaluronan: the common role in breast cancer. Biomed Res Int (2014) 2014:606458. doi:10.1155/2014/606458
25. West DC, Hampson IN, Arnold F, Kumar S. Angiogenesis induced by degradation products of hyaluronic acid. Science (1985) 228:1324-6. doi:10.1126/science.2408340
26. Hawkins CL, Davies MJ. Degradation of hyaluronic acid, poly-and monosaccharides, and model compounds by hypochlorite: evidence for radical intermediates and fragmentation. Free Radic Biol Med (1998) 24:1396-410. doi:10.1016/S0891-5849(98)00009-4
27. Rosines E, Schmidt HJ, Nigam SK. The effect of hyaluronic acid size and concentration on branching morphogenesis and tubule differentiation in developing kidney culture systems: potential applications to engineering of renal tissues. Biomaterials (2007) 28:4806-17. doi:10.1016/j.biomaterials.2007.07.034
28. Dang S, Peng Y, Ye L, Wang Y, Qian Z, Chen Y, et al. Stimulation of TLR4 by LMW-HA induces metastasis in human papillary thyroid carcinoma through CXCR7. Clin Dev Immunol (2013) 2013:712561. doi:10.1155/2013/712561
29. Suzuki M, Kobayashi H, Kanayama N, Nishida T, Takigawa M, Terao T. CD44 stimulation by fragmented hyaluronic acid induces upregulation and tyrosine phosphorylation of c-Met receptor protein in human chondrosarcoma cells. Biochim Biophys Acta (2002) 1591:37-44. doi:10.1016/S0167-4889(02)00246-X
30. Sugahara KN, Hirata T, Hayasaka H, Stern R, Murai T, Miyasaka M. Tumor cells enhance their own CD44 cleavage and motility by generating hyaluronan fragments. J Biol Chem (2006) 281:5861-8. doi:10.1074/jbc. M506740200
31. Hosono K, Nishida Y, Knudson W, Knudson CB, Naruse T, Suzuki Y, et al. Hyaluronan oligosaccharides inhibit tumorigenicity of osteosarcoma cell lines MG-63 and LM-8 in vitro and in vivo via perturbation of hyaluronan-rich pericellular matrix of the cells. Am J Pathol (2007) 171:274-86. doi:10.2353/ajpath.2007.060828
32. Khaldoyanidi SK, Goncharova V, Mueller B, Schraufstatter IU. Hyaluronan in the healthy and malignant hematopoietic microenvironment. Adv Cancer Res (2014) 123:149-89. doi:10.1016/B978-0-12-800092-2.00006-X
33. Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, et al. Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem (1999) 274:25085-92. doi:10.1074/jbc.274.35.25085
34. Mohamadzadeh M, DeGrendele H, Arizpe H, Estess P, Siegelman M. Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion. J Clin Invest (1998) 101:97-108. doi:10.1172/JCI1604
35. Wilkinson TS, Potter-Perigo S, Tsoi C, Altman LC, Wight TN. Pro-and anti-inflammatory factors cooperate to control hyaluronan synthesis in lung fibroblasts. Am J Respir Cell Mol Biol (2004) 31:92-9. doi:10.1165/rcmb.2003-0380OC
36. Vigetti D, Genasetti A, Karousou E, Viola M, Moretto P, Clerici M, et al. Proinflammatory cytokines induce hyaluronan synthesis and monocyte adhesion in human endothelial cells through hyaluronan synthase 2 (HAS2) and the nuclear factor-kappaB (NF-kappaB) pathway. J Biol Chem (2010) 285:24639-45. doi:10.1074/jbc. M110.134536
37. Estess P, Nandi A, Mohamadzadeh M, Siegelman MH. Interleukin 15 induces endothelial hyaluronan expression in vitro and promotes activated T cell extravasation through a CD44-dependent pathway in vivo. J Exp Med (1999) 190:9-19. doi:10.1084/jem.190.1.9
38. Stuhlmeier KM, Pollaschek C. Differential effect of transforming growth factor beta (TGF-beta) on the genes encoding hyaluronan synthases and utilization of the p38 MAPK pathway in TGF-beta-induced hyaluronan synthase 1 activation. J Biol Chem (2004) 279:8753-60. doi:10.1074/jbc. M303945200
39. Jacobson A, Brinck J, Briskin MJ, Spicer AP, Heldin P. Expression of human hyaluronan synthases in response to external stimuli. Biochem J (2000) 348(Pt 1):29-35. doi:10.1042/0264-6021:3480029
40. Heldin P, Asplund T, Ytterberg D, Thelin S, Laurent TC. Characterization of the molecular mechanism involved in the activation of hyaluronan synthetase by platelet-derived growth factor in human mesothelial cells. Biochem J (1992) 283(Pt 1):165-70.
41. Monslow J, Sato N, Mack JA, Maytin EV. Wounding-induced synthesis of hyaluronic acid in organotypic epidermal cultures requires the release of heparin-binding egf and activation of the EGFR. J Invest Dermatol (2009) 129:2046-58. doi:10.1038/jid.2009.9
42. Pienimaki JP, Rilla K, Fulop C, Sironen RK, Karvinen S, Pasonen S, et al. Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan. J Biol Chem (2001) 276:20428-35. doi:10.1074/jbc. M007601200
43. Yamane T, Kobayashi-Hattori K, Oishi Y. Adiponectin promotes hyaluronan synthesis along with increases in hyaluronan synthase 2 transcripts through an AMP-activated protein kinase/peroxisome proliferator-activated receptor-a-dependent pathway in human dermal fibroblasts. Biochem Biophys Res Commun (2011) 415:235-8. doi:10.1016/j.bbrc.2011.09.151
44. Bourguignon LYW, Gilad E, Peyrollier K. Heregulin-mediated ErbB2-ERK signaling activates hyaluronan synthases leading to CD44-dependent ovarian tumor cell growth and migration. J Biol Chem (2007) 282:19426-41. doi:10.1074/jbc. M610054200
45. Vigetti D, Deleonibus S, Moretto P, Karousou E, Viola M, Bartolini B, et al. Role of UDP-N-acetylglucosamine (GlcNAc) and O-GlcNAcylation of hyaluronan synthase 2 in the control of chondroitin sulfate and hyaluronan synthesis. J Biol Chem (2012) 287:35544-55. doi:10.1074/jbc. M112.402347
46. Karousou E, Kamiryo M, Skandalis SS, Ruusala A, Asteriou T, Passi A, et al. The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination. J Biol Chem (2010) 285:23647-54. doi:10.1074/jbc. M110.127050
47. Vigetti D, Karousou E, Viola M, Deleonibus S, De Luca G, Passi A. Hyaluronan: biosynthesis and signaling. Biochim Biophys Acta (2014) 1840:2452-9. doi:10.1016/j.bbagen.2014.02.001
48. Michael DR, Phillips AO, Krupa A, Martin J, Redman JE, Altaher A, et al. The human hyaluronan synthase 2 (HAS2) gene and its natural antisense RNA exhibit coordinated expression in the renal proximal tubular epithelial cell. J Biol Chem (2011) 286:19523-32. doi:10.1074/jbc. M111.233916
49. Stern R, Jedrzejas MJ. Hyaluronidases: their genomics, structures, and mechanisms of action. Chem Rev (2006) 106:818-39. doi:10.1021/cr050247k
50. Mochizuki S, Kano A, Shimada N, Maruyama A. Uptake of enzymatically-digested hyaluronan by liver endothelial cells in vivo and in vitro. J Biomater Sci Polym Ed (2009) 20:83-97. doi:10.1163/156856208X393518
51. Armstrong SE, Bell DR. Relationship between lymph and tissue hyaluronan in skin and skeletal muscle. Am J Physiol Heart Circ Physiol (2002) 283:H2485-94. doi:10.1152/ajpheart.00385.2002
52. Culty M, Nguyen HA, Underhill CB. The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan. J Cell Biol (1992) 116:1055-62. doi:10.1083/jcb.116.4.1055
53. Csoka AB, Frost GI, Stern R. The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol (2001) 20:499-508. doi:10.1016/S0945-053X(01)00172-X
54. Lepperdinger G, Strobl B, Kreil G. HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity. J Biol Chem (1998) 273:22466-70. doi:10.1074/jbc.273.35.22466
55. Harada H, Takahashi M. CD44-dependent intracellular and extracellular catabolism of hyaluronic acid by hyaluronidase-1 and-2. J Biol Chem (2007) 282:5597-607. doi:10.1074/jbc. M608358200
56. Cherr GN, Meyers SA, Yudin AI, VandeVoort CA, Myles DG, Primakoff P, et al. The PH-20 protein in cynomolgus macaque spermatozoa: identification of two different forms exhibiting hyaluronidase activity. Dev Biol (1996) 175:142-53. doi:10.1006/dbio.1996.0102
57. Bates EJ, Harper GS, Lowther DA, Preston BN. Effect of oxygen-derived reactive species on cartilage proteoglycan-hyaluronate aggregates. Biochem Int (1984) 8:629-37.
58. Karbownik MS, Nowak JZ. Hyaluronan: towards novel anti-cancer therapeutics. Pharmacol Rep (2013) 65:1056-74. doi:10.1016/S1734-1140(13)71465-8
59. Soltés L, Kogan G, Stankovska M, Mendichi R, Rychlỳ J, Schiller J, et al. Degradation of high-molar-mass hyaluronan and characterization of fragments. Biomacromolecules (2007) 8:2697-705. doi:10.1021/bm070309b
60. McNeil JD, Wiebkin OW, Betts WH, Cleland LG. Depolymerisation products of hyaluronic acid after exposure to oxygen-derived free radicals. Ann Rheum Dis (1985) 44:780-9. doi:10.1136/ard.44.11.780
61. Atmuri V, Martin DC, Hemming R, Gutsol A, Byers S, Sahebjam S, et al. Hyaluronidase 3 (HYAL3) knockout mice do not display evidence of hyaluronan accumulation. Matrix Biol (2008) 27:653-60. doi:10.1016/j.matbio.2008.07.006
62. Hemming R, Martin DC, Slominski E, Nagy JI, Halayko AJ, Pind S, et al. Mouse Hyal3 encodes a 45-to 56-kDa glycoprotein whose overexpression increases hyaluronidase 1 activity in cultured cells. Glycobiology (2008) 18:280-9. doi:10.1093/glycob/cwn006
63. Natowicz MR, Short MP, Wang Y, Dickersin GR, Gebhardt MC, Rosenthal DI, et al. Clinical and biochemical manifestations of hyaluronidase deficiency. N Engl J Med (1996) 335:1029-33. doi:10.1056/NEJM199610033351405
64. De la Motte C, Nigro J, Vasanji A, Rho H, Kessler S, Bandyopadhyay S, et al. Platelet-derived hyaluronidase 2 cleaves hyaluronan into fragments that trigger monocyte-mediated production of proinflammatory cytokines. Am J Pathol (2009) 174:2254-64. doi:10.2353/ajpath.2009.080831
65. Girard N, Maingonnat C, Bertrand P, Tilly H, Vannier J-P, Delpech B. Human monocytes synthesize hyaluronidase. Br J Haematol (2002) 119:199-203. doi:10.1046/j.1365-2141.2002.03733.x
66. Bot PT, Pasterkamp G, Goumans M-J, Strijder C, Moll FL, de Vries J-P, et al. Hyaluronic acid metabolism is increased in unstable plaques. Eur J Clin Invest (2010) 40:818-27. doi:10.1111/j.1365-2362.2010.02326.x
67. Chajara A, Raoudi M, Delpech B, Leroy M, Basuyau JP, Levesque H. Increased hyaluronan and hyaluronidase production and hyaluronan degradation in injured aorta of insulin-resistant rats. Arterioscler Thromb Vasc Biol (2000) 20:1480-7. doi:10.1161/01.ATV.20.6.1480
68. Chowdhury B, Hemming R, Hombach-Klonisch S, Flamion B, Triggs-Raine B. Murine hyaluronidase 2 deficiency results in extracellular hyaluronan accumulation and severe cardiopulmonary dysfunction. J Biol Chem (2013) 288:520-8. doi:10.1074/jbc. M112.393629
69. Ormiston ML, Slaughter GRD, Deng Y, Stewart DJ, Courtman DW. The enzymatic degradation of hyaluronan is associated with disease progression in experimental pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol (2010) 298:L148-57. doi:10.1152/ajplung.00097.2009
70. Klagas I, Goulet S, Karakiulakis G, Zhong J, Baraket M, Black JL, et al. Decreased hyaluronan in airway smooth muscle cells from patients with asthma and COPD. Eur Respir J (2009) 34:616-28. doi:10.1183/09031936.00070808
71. Dentener MA, Vernooy JHJ, Hendriks S, Wouters EFM. Enhanced levels of hyaluronan in lungs of patients with COPD: relationship with lung function and local inflammation. Thorax (2005) 60:114-9. doi:10.1136/thx.2003.020842
72. Monzon ME, Fregien N, Schmid N, Falcon NS, Campos M, Casalino-Matsuda SM, et al. Reactive oxygen species and hyaluronidase 2 regulate airway epithelial hyaluronan fragmentation. J Biol Chem (2010) 285:26126-34. doi:10.1074/jbc. M110.135194
73. Bracke KR, Dentener MA, Papakonstantinou E, Vernooy JHJ, Demoor T, Pauwels NS, et al. Enhanced deposition of low-molecular-weight hyaluronan in lungs of cigarette smoke-exposed mice. Am J Respir Cell Mol Biol (2010) 42:753-61. doi:10.1165/rcmb.2008-0424OC
74. Eldridge L, Moldobaeva A, Wagner EM. Increased hyaluronan fragmentation during pulmonary ischemia. Am J Physiol Lung Cell Mol Physiol (2011) 301:L782-8. doi:10.1152/ajplung.00079.2011
75. Rauhala L, Hämäläinen L, Salonen P, Bart G, Tammi M, Pasonen-Seppänen S, et al. Low dose ultraviolet B irradiation increases hyaluronan synthesis in epidermal keratinocytes via sequential induction of hyaluronan synthases Has1-3 mediated by p38 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling. J Biol Chem (2013) 288:17999-8012. doi:10.1074/jbc. M113.472530
76. Poole AR, Witter J, Roberts N, Piccolo F, Brandt R, Paquin J, et al. Inflammation and cartilage metabolism in rheumatoid arthritis. Studies of the blood markers hyaluronic acid, orosomucoid, and keratan sulfate. Arthritis Rheum (1990) 33:790-9. doi:10.1002/art.1780330605
77. Campo GM, Avenoso A, D'Ascola A, Scuruchi M, Prestipino V, Nastasi G, et al. The inhibition of hyaluronan degradation reduced pro-inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-induced arthritis. J Cell Biochem (2012) 113:1852-67. doi:10.1002/jcb.24054
78. Bouga H, Tsouros I, Bounias D, Kyriakopoulou D, Stavropoulos MS, Papageorgakopoulou N, et al. Involvement of hyaluronidases in colorectal cancer. BMC Cancer (2010) 10:499. doi:10.1186/1471-2407-10-499
79. Tan J-X, Wang X-Y, Su X-L, Li H-Y, Shi Y, Wang L, et al. Upregulation of HYAL1 expression in breast cancer promoted tumor cell proliferation, migration, invasion and angiogenesis. PLoS One (2011) 6:e22836. doi:10.1371/journal.pone.0022836
80. Delpech B, Courel MN, Maingonnat C, Chauzy C, Sesboüé R, Pratesi G. Hyaluronan digestion and synthesis in an experimental model of metastatic tumour. Histochem J (2001) 33:553-8. doi:10.1023/A:1014908009409
81. Franzmann EJ, Schroeder GL, Goodwin WJ, Weed DT, Fisher P, Lokeshwar VB. Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors. Int J Cancer (2003) 106:438-45. doi:10.1002/ijc.11252
82. Lokeshwar VB, Cerwinka WH, Isoyama T, Lokeshwar BL. HYAL1 hyaluronidase in prostate cancer: a tumor promoter and suppressor. Cancer Res (2005) 65:7782-9. doi:10.1158/0008-5472.CAN-05-1022
83. Delpech B, Laquerriere A, Maingonnat C, Bertrand P, Freger P. Hyaluronidase is more elevated in human brain metastases than in primary brain tumours. Anticancer Res (2002) 22:2423-7.
84. Simpson MA, Lokeshwar VB. Hyaluronan and hyaluronidase in genitourinary tumors. Front Biosci (2008) 13:5664-80. doi:10.2741/3108
85. Eissa S, Shehata H, Mansour A, Esmat M, El-Ahmady O. Detection of hyaluronidase RNA and activity in urine of schistosomal and non-schistosomal bladder cancer. Med Oncol (2012) 29:3345-51. doi:10.1007/s12032-012-0295-8
86. Yoffou PH, Edjekouane L, Meunier L, Tremblay A, Provencher DM, Mes-Masson A-M, et al. Subtype specific elevated expression of hyaluronidase-1 (HYAL-1) in epithelial ovarian cancer. PLoS One (2011) 6:e20705. doi:10.1371/journal.pone.0020705
87. Nykopp TK, Rilla K, Tammi MI, Tammi RH, Sironen R, Hämäläinen K, et al. Hyaluronan synthases (HAS1-3) and hyaluronidases (HYAL1-2) in the accumulation of hyaluronan in endometrioid endometrial carcinoma. BMC Cancer (2010) 10:512. doi:10.1186/1471-2407-10-512
88. Frost GI, Mohapatra G, Wong TM, Csóka AB, Gray JW, Stern R. HYAL1LUCA-1, a candidate tumor suppressor gene on chromosome 3p21.3, is inactivated in head and neck squamous cell carcinomas by aberrant splicing of pre-mRNA. Oncogene (2000) 19:870-7. doi:10.1038/sj.onc.1203317
89. Zabarovsky ER, Lerman MI, Minna JD. Tumor suppressor genes on chromosome 3p involved in the pathogenesis of lung and other cancers. Oncogene (2002) 21:6915-35. doi:10.1038/sj.onc.1205835
90. Jacobson A, Rahmanian M, Rubin K, Heldin P. Expression of hyaluronan synthase 2 or hyaluronidase 1 differentially affect the growth rate of transplantable colon carcinoma cell tumors. Int J Cancer (2002) 102:212-9. doi:10.1002/ijc.10683
91. Shuster S, Frost GI, Csoka AB, Formby B, Stern R. Hyaluronidase reduces human breast cancer xenografts in SCID mice. Int J Cancer (2002) 102:192-7. doi:10.1002/ijc.10668
92. Provenzano PP, Cuevas C, Chang AE, Goel VK, Von Hoff DD, Hingorani SR. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell (2012) 21:418-29. doi:10.1016/j.ccr.2012.01.007
93. Bharadwaj AG, Kovar JL, Loughman E, Elowsky C, Oakley GG, Simpson MA. Spontaneous metastasis of prostate cancer is promoted by excess hyaluronan synthesis and processing. Am J Pathol (2009) 174:1027-36. doi:10.2353/ajpath.2009.080501
94. Udabage L, Brownlee GR, Waltham M, Blick T, Walker EC, Heldin P, et al. Antisense-mediated suppression of hyaluronan synthase 2 inhibits the tumorigenesis and progression of breast cancer. Cancer Res (2005) 65:6139-50. doi:10.1158/0008-5472.CAN-04-1622
95. Coleman PJ, Scott D, Mason RM, Levick JR. Characterization of the effect of high molecular weight hyaluronan on trans-synovial flow in rabbit knees. J Physiol (1999) 514(Pt 1):265-82. doi:10.1111/j.1469-7793.1999.265af.x
96. Wang T, Cheng HH, Heimbürger O, Chen C, Waniewski J, Bergström J, et al. Hyaluronan decreases peritoneal fluid absorption: effect of molecular weight and concentration of hyaluronan. Kidney Int (1999) 55:667-73. doi:10.1046/j.1523-1755.1999.00279.x
97. Margolis RU, Margolis RK, Chang LB, Preti C. Glycosaminoglycans of brain during development. Biochemistry (1975) 14:85-8. doi:10.1021/bi00672a014
98. Matsumoto K, Li Y, Jakuba C, Sugiyama Y, Sayo T, Okuno M, et al. Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb. Development (2009) 136:2825-35. doi:10.1242/dev.038505
99. Camenisch TD, Spicer AP, Brehm-Gibson T, Biesterfeldt J, Augustine ML, Calabro A, et al. Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. J Clin Invest (2000) 106:349-60. doi:10.1172/JCI10272
100. Chopra A, Murray ME, Byfield FJ, Mendez MG, Halleluyan R, Restle DJ, et al. Augmentation of integrin-mediated mechanotransduction by hyaluronic acid. Biomaterials (2014) 35:71-82. doi:10.1016/j.biomaterials.2013.09.066
101. Travis JA, Hughes MG, Wong JM, Wagner WD, Geary RL. Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: role of CD44 and implications for constrictive remodeling. Circ Res (2001) 88:77-83. doi:10.1161/01.RES.88.1.77
102. Gouëffic Y, Guilluy C, Guérin P, Patra P, Pacaud P, Loirand G. Hyaluronan induces vascular smooth muscle cell migration through RHAMM-mediated PI3K-dependent Rac activation. Cardiovasc Res (2006) 72:339-48. doi:10.1016/j.cardiores.2006.07.017
103. Chen C-H, Wang S-S, Wei EI, Chu T-Y, Hsieh PCH. Hyaluronan enhances bone marrow cell therapy for myocardial repair after infarction. Mol Ther (2013) 21:670-9. doi:10.1038/mt.2012.268
104. Craig EA, Parker P, Camenisch TD. Size-dependent regulation of Snail2 by hyaluronan: its role in cellular invasion. Glycobiology (2009) 19:890-8. doi:10.1093/glycob/cwp064
105. Bourguignon LYW, Wong G, Xia W, Man M-Q, Holleran WM, Elias PM. Selective matrix (hyaluronan) interaction with CD44 and RhoGTPase signaling promotes keratinocyte functions and overcomes age-related epidermal dysfunction. J Dermatol Sci (2013) 72:32-44. doi:10.1016/j.jdermsci.2013.05.003
106. Passi A, Sadeghi P, Kawamura H, Anand S, Sato N, White LE, et al. Hyaluronan suppresses epidermal differentiation in organotypic cultures of rat keratinocytes. Exp Cell Res (2004) 296:123-34. doi:10.1016/j.yexcr.2004.01.031
107. Arnold F, Jia C, He C, Cherry GW, Carbow B, Meyer-Ingold W, et al. Hyaluronan, heterogeneity, and healing: the effects of ultrapure hyaluronan of defined molecular size on the repair of full-thickness pig skin wounds. Wound Repair Regen (1995) 3:299-310. doi:10.1046/j.1524-475X.1995.30310.x
108. Galeano M, Polito F, Bitto A, Irrera N, Campo GM, Avenoso A, et al. Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice. Biochim Biophys Acta (2011) 1812:752-9. doi:10.1016/j.bbadis.2011.03.012
109. Khaing ZZ, Milman BD, Vanscoy JE, Seidlits SK, Grill RJ, Schmidt CE. High molecular weight hyaluronic acid limits astrocyte activation and scar formation after spinal cord injury. J Neural Eng (2011) 8:046033. doi:10.1088/1741-2560/8/4/046033
110. Ferns GA, Konneh M, Rutherford C, Woolaghan E, Anggard EE. Hyaluronan (HYAL-BV 5200) inhibits neo-intimal macrophage influx after balloon-catheter induced injury in the cholesterol-fed rabbit. Atherosclerosis (1995) 114:157-64. doi:10.1016/0021-9150(94)05479-3
111. Kothapalli D, Zhao L, Hawthorne EA, Cheng Y, Lee E, Puré E, et al. Hyaluronan and CD44 antagonize mitogen-dependent cyclin D1 expression in mesenchymal cells. J Cell Biol (2007) 176:535-44. doi:10.1083/jcb.200611058
112. Vigetti D, Rizzi M, Moretto P, Deleonibus S, Dreyfuss JM, Karousou E, et al. Glycosaminoglycans and glucose prevent apoptosis in 4-methylumbelliferone-treated human aortic smooth muscle cells. J Biol Chem (2011) 286:34497-503. doi:10.1074/jbc. M111.266312
113. Liu Y-Y, Lee C-H, Dedaj R, Zhao H, Mrabat H, Sheidlin A, et al. High-molecular-weight hyaluronan-a possible new treatment for sepsis-induced lung injury: a preclinical study in mechanically ventilated rats. Crit Care (2008) 12:R102. doi:10.1186/cc6982
114. Nakamura K, Yokohama S, Yoneda M, Okamoto S, Tamaki Y, Ito T, et al. High, but not low, molecular weight hyaluronan prevents T-cell-mediated liver injury by reducing proinflammatory cytokines in mice. J Gastroenterol (2004) 39:346-54. doi:10.1007/s00535-003-1301-x
115. Fuchs K, Hippe A, Schmaus A, Homey B, Sleeman JP, Orian-Rousseau V. Opposing effects of high-and low-molecular weight hyaluronan on CXCL12-induced CXCR4 signaling depend on CD44. Cell Death Dis (2013) 4:e819. doi:10.1038/cddis.2013.364
116. Asari A, Kanemitsu T, Kurihara H. Oral administration of high molecular weight hyaluronan (900 kDa) controls immune system via toll-like receptor 4 in the intestinal epithelium. J Biol Chem (2010) 285:24751-8. doi:10.1074/jbc. M110.104950
117. Schommer NN, Muto J, Nizet V, Gallo RL. Hyaluronan breakdown contributes to immune defense against group A Streptococcus. J Biol Chem (2014) 289:26914-21. doi:10.1074/jbc. M114.575621
118. Mueller BM, Schraufstatter IU, Goncharova V, Povaliy T, DiScipio R, Khaldoyanidi SK. Hyaluronan inhibits postchemotherapy tumor regrowth in a colon carcinoma xenograft model. Mol Cancer Ther (2010) 9:3024-32. doi:10.1158/1535-7163.MCT-10-0529
119. Chang C-C, Hsieh M-S, Liao S-T, Chen Y-H, Cheng C-W, Huang P-T, et al. Hyaluronan regulates PPARγ and inflammatory responses in IL-1β-stimulated human chondrosarcoma cells, a model for osteoarthritis. Carbohydr Polym (2012) 90:1168-75. doi:10.1016/j.carbpol.2012.06.071
120. Berdiaki A, Nikitovic D, Tsatsakis A, Katonis P, Karamanos NK, Tzanakakis GN. bFGF induces changes in hyaluronan synthase and hyaluronidase isoform expression and modulates the migration capacity of fibrosarcoma cells. Biochim Biophys Acta (2009) 1790:1258-65. doi:10.1016/j.bbagen.2009.06.013
121. Chanmee T, Ontong P, Mochizuki N, Kongtawelert P, Konno K, Itano N. Excessive hyaluronan production promotes acquisition of cancer stem cell signatures through the coordinated regulation of twist and the transforming growth factor β (TGF-β)-Snail signaling axis. J Biol Chem (2014) 289:26038-56. doi:10.1074/jbc. M114.564120
122. Termeer CC, Hennies J, Voith U, Ahrens T, Weiss JM, Prehm P, et al. Oligosaccharides of hyaluronan are potent activators of dendritic cells. J Immunol (2000) 165:1863-70. doi:10.4049/jimmunol.165.4.1863
123. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, et al. Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4. J Exp Med (2002) 195:99-111. doi:10.1084/jem.20001858
124. Tabata T, Mine S, Okada Y, Tanaka Y. Low molecular weight hyaluronan increases the uptaking of oxidized LDL into monocytes. Endocr J (2007) 54:685-93. doi:10.1507/endocrj. K05-120
125. Cui X, Xu H, Zhou S, Zhao T, Liu A, Guo X, et al. Evaluation of angiogenic activities of hyaluronan oligosaccharides of defined minimum size. Life Sci (2009) 85:573-7. doi:10.1016/j.lfs.2009.08.010
126. Ibrahim S, Ramamurthi A. Hyaluronic acid cues for functional endothelialization of vascular constructs. J Tissue Eng Regen Med (2008) 2:22-32. doi:10.1002/term.61
127. Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL. Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem (2004) 279:17079-84. doi:10.1074/jbc. M310859200
128. McCourt PA, Ek B, Forsberg N, Gustafson S. Intercellular adhesion molecule-1 is a cell surface receptor for hyaluronan. J Biol Chem (1994) 269:30081-4.
129. Deed R, Rooney P, Kumar P, Norton JD, Smith J, Freemont AJ, et al. Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan. Int J Cancer (1997) 71:251-6. doi:10.1002/(SICI)1097-0215(19970410)71:2<251::AID-IJC21>3.0.CO;2-J
130. Campo GM, Avenoso A, D'Ascola A, Scuruchi M, Prestipino V, Calatroni A, et al. Hyaluronan in part mediates IL-1beta-induced inflammation in mouse chondrocytes by up-regulating CD44 receptors. Gene (2012) 494:24-35. doi:10.1016/j.gene.2011.11.064
131. Sylvester A, Sivaraman B, Deb P, Ramamurthi A. Nanoparticles for localized delivery of hyaluronan oligomers towards regenerative repair of elastic matrix. Acta Biomater (2013) 9:9292-302. doi:10.1016/j.actbio.2013.07.032
132. Tolg C, Telmer P, Turley E. Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair. PLoS One (2014) 9:e88479. doi:10.1371/journal.pone.0088479
133. Gao F, Liu Y, He Y, Yang C, Wang Y, Shi X, et al. Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis. Matrix Biol (2010) 29:107-16. doi:10.1016/j.matbio.2009.11.002
134. Kothapalli CR, Taylor PM, Smolenski RT, Yacoub MH, Ramamurthi A. Transforming growth factor beta 1 and hyaluronan oligomers synergistically enhance elastin matrix regeneration by vascular smooth muscle cells. Tissue Eng Part A (2009) 15:501-11. doi:10.1089/ten.tea.2008.0040
135. Chajara A, Raoudi M, Delpech B, Levesque H. Inhibition of arterial cells proliferation in vivo in injured arteries by hyaluronan fragments. Atherosclerosis (2003) 171:15-9. doi:10.1016/S0021-9150(03)00303-4
136. Xu H, Ito T, Tawada A, Maeda H, Yamanokuchi H, Isahara K, et al. Effect of hyaluronan oligosaccharides on the expression of heat shock protein 72. J Biol Chem (2002) 277:17308-14. doi:10.1074/jbc. M112371200
137. Selbi W, de la Motte CA, Hascall VC, Day AJ, Bowen T, Phillips AO. Characterization of hyaluronan cable structure and function in renal proximal tubular epithelial cells. Kidney Int (2006) 70:1287-95. doi:10.1038/sj.ki.5001760
138. Lauer ME, Glant TT, Mikecz K, DeAngelis PL, Haller FM, Husni ME, et al. Irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor necrosis factor-stimulated gene-6. J Biol Chem (2013) 288:205-14. doi:10.1074/jbc. M112.403998
139. Bourguignon LYW, Wong G, Earle CA, Xia W. Interaction of low molecular weight hyaluronan with CD44 and toll-like receptors promotes the actin filament-associated protein 110-actin binding and MyD88-NFκB signaling leading to proinflammatory cytokine/chemokine production and breast tumor invasion. Cytoskeleton (Hoboken) (2011) 68:671-93. doi:10.1002/cm.20544
140. Fieber C, Baumann P, Vallon R, Termeer C, Simon JC, Hofmann M, et al. Hyaluronan-oligosaccharide-induced transcription of metalloproteases. J Cell Sci (2004) 117:359-67. doi:10.1242/jcs.00831
141. Toole BP, Ghatak S, Misra S. Hyaluronan oligosaccharides as a potential anticancer therapeutic. Curr Pharm Biotechnol (2008) 9:249-52. doi:10.2174/138920108785161569
142. Zeng C, Toole BP, Kinney SD, Kuo JW, Stamenkovic I. Inhibition of tumor growth in vivo by hyaluronan oligomers. Int J Cancer (1998) 77:396-401. doi:10.1002/(SICI)1097-0215(19980729)77:3<396::AID-IJC15>3.3.CO;2-W
143. Ghatak S, Misra S, Toole BP. Hyaluronan oligosaccharides inhibit anchorage-independent growth of tumor cells by suppressing the phosphoinositide 3-kinase/Akt cell survival pathway. J Biol Chem (2002) 277:38013-20. doi:10.1074/jbc. M202404200
144. Wiranowska M, Ladd S, Moscinski LC, Hill B, Haller E, Mikecz K, et al. Modulation of hyaluronan production by CD44 positive glioma cells. Int J Cancer (2010) 127:532-42. doi:10.1002/ijc.25085
145. Gilg AG, Tye SL, Tolliver LB, Wheeler WG, Visconti RP, Duncan JD, et al. Targeting hyaluronan interactions in malignant gliomas and their drug-resistant multipotent progenitors. Clin Cancer Res (2008) 14:1804-13. doi:10.1158/1078-0432.CCR-07-1228
146. Kujawa MJ, Carrino DA, Caplan AI. Substrate-bonded hyaluronic acid exhibits a size-dependent stimulation of chondrogenic differentiation of stage 24 limb mesenchymal cells in culture. Dev Biol (1986) 114:519-28. doi:10.1016/0012-1606(86)90214-9
147. Park JU, Tsuchiya T. Increase in gap junctional intercellular communication by high molecular weight hyaluronic acid associated with fibroblast growth factor 2 and keratinocyte growth factor production in normal human dermal fibroblasts. Tissue Eng (2002) 8:419-27. doi:10.1089/107632702760184682
148. Ghazi K, Deng-Pichon U, Warnet J-M, Rat P. Hyaluronan fragments improve wound healing on in vitro cutaneous model through P2X7 purinoreceptor basal activation: role of molecular weight. PLoS One (2012) 7:e48351. doi:10.1371/journal.pone.0048351
149. Joddar B, Ramamurthi A. Fragment size-and dose-specific effects of hyaluronan on matrix synthesis by vascular smooth muscle cells. Biomaterials (2006) 27:2994-3004. doi:10.1016/j.biomaterials.2006.01.020
150. Damodarasamy M, Johnson RS, Bentov I, MacCoss MJ, Vernon RB, Reed MJ. Hyaluronan enhances wound repair and increases collagen III in aged dermal wounds. Wound Repair Regen (2014) 22:521-6. doi:10.1111/wrr.12192
151. Kaya G, Tran C, Sorg O, Hotz R, Grand D, Carraux P, et al. Hyaluronate fragments reverse skin atrophy by a CD44-dependent mechanism. PLoS Med (2006) 3:e493. doi:10.1371/journal.pmed.0030493
152. Trabucchi E, Pallotta S, Morini M, Corsi F, Franceschini R, Casiraghi A, et al. Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing. Int J Tissue React (2002) 24:65-71.
153. Scuri M, Abraham WM, Botvinnikova Y, Forteza R. Hyaluronic acid blocks porcine pancreatic elastase (PPE)-induced bronchoconstriction in sheep. Am J Respir Crit Care Med (2001) 164:1855-9. doi:10.1164/ajrccm.164.10.2011115
154. Cantor JO, Shteyngart B, Cerreta JM, Liu M, Armand G, Turino GM. The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo. Proc Soc Exp Biol Med (2000) 225:65-71. doi:10.1046/j.1525-1373.2000.22508.x
155. Garantziotis S, Li Z, Potts EN, Kimata K, Zhuo L, Morgan DL, et al. Hyaluronan mediates ozone-induced airway hyperresponsiveness in mice. J Biol Chem (2009) 284:11309-17. doi:10.1074/jbc. M802400200
156. Leu S-W, Shi L, Xu C, Zhao Y, Liu B, Li Y, et al. TLR4 through IFN-β promotes low molecular mass hyaluronan-induced neutrophil apoptosis. J Immunol (2011) 186:556-62. doi:10.4049/jimmunol.1001630
157. Onoda M, Nakaseko C, Yokota A, Saito Y. Ligation of CD44 with low-molecular-weight hyaluronan and a monoclonal antibody leads to inhibition of drug-induced apoptosis in a human myeloid cell line. Hematology (2009) 14:213-9. doi:10.1179/102453309X426236
158. Wolf D, Schümann J, Koerber K, Kiemer AK, Vollmar AM, Sass G, et al. Low-molecular-weight hyaluronic acid induces nuclear factor-kappaB-dependent resistance against tumor necrosis factor alpha-mediated liver injury in mice. Hepatology (2001) 34:535-47. doi:10.1053/jhep.2001.27218
159. Hill DR, Kessler SP, Rho HK, Cowman MK, de la Motte CA. Specific-sized hyaluronan fragments promote expression of human β-defensin 2 in intestinal epithelium. J Biol Chem (2012) 287:30610-24. doi:10.1074/jbc. M112.356238
160. Collins SL, Black KE, Chan-Li Y, Ahn Y-H, Cole PA, Powell JD, et al. Hyaluronan fragments promote inflammation by down-regulating the anti-inflammatory A2a receptor. Am J Respir Cell Mol Biol (2011) 45:675-83. doi:10.1165/rcmb.2010-0387OC
161. Pandey MS, Baggenstoss BA, Washburn J, Harris EN, Weigel PH. The hyaluronan receptor for endocytosis (HARE) activates NF-κB-mediated gene expression in response to 40-400-kDa, but not smaller or larger, hyaluronans. J Biol Chem (2013) 288:14068-79. doi:10.1074/jbc. M112.442889
162. Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol (2006) 177:1272-81. doi:10.4049/jimmunol.177.2.1272
163. Schraufstatter I, Serobyan N, DiScipio R, Feofanova N, Orlovskaya I, Khaldoyanidi SK. Hyaluronan stimulates mobilization of mature hematopoietic cells but not hematopoietic progenitors. J Stem Cells (2009) 4:191-202. doi:jsc.2010.4.4.191
164. Lyle DB, Breger JC, Baeva LF, Shallcross JC, Durfor CN, Wang NS, et al. Low molecular weight hyaluronic acid effects on murine macrophage nitric oxide production. J Biomed Mater Res A (2010) 94:893-904. doi:10.1002/jbm.a.32760
165. Hodge-Dufour J, Noble PW, Horton MR, Bao C, Wysoka M, Burdick MD, et al. Induction of IL-12 and chemokines by hyaluronan requires adhesion-dependent priming of resident but not elicited macrophages. J Immunol (1997) 159:2492-500.
166. McKee CM, Penno MB, Cowman M, Burdick MD, Strieter RM, Bao C, et al. Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44. J Clin Invest (1996) 98:2403-13. doi:10.1172/JCI119054
167. Sokolowska M, Chen L-Y, Eberlein M, Martinez-Anton A, Liu Y, Alsaaty S, et al. Low molecular weight hyaluronan activates cytosolic phospholipase A2a and eicosanoid production in monocytes and macrophages. J Biol Chem (2014) 289:4470-88. doi:10.1074/jbc. M113.515106
168. Kuang D-M, Wu Y, Chen N, Cheng J, Zhuang S-M, Zheng L. Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes. Blood (2007) 110:587-95. doi:10.1182/blood-2007-01-068031
169. Boodoo S, Spannhake EW, Powell JD, Horton MR. Differential regulation of hyaluronan-induced IL-8 and IP-10 in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol (2006) 291:L479-86. doi:10.1152/ajplung.00518.2005
170. Ochoa CD, Garg HG, Hales CA, Quinn DA. Low molecular weight hyaluronan, via AP-1 and NF-κB signalling, induces IL-8 in transformed bronchial epithelial cells. Swiss Med Wkly (2011) 141:w13255. doi:10.4414/smw.2011.13255
171. Campo GM, Avenoso A, Campo S, D'Ascola A, Traina P, Calatroni A. Differential effect of molecular size HA in mouse chondrocytes stimulated with PMA. Biochim Biophys Acta (2009) 1790:1353-67. doi:10.1016/j.bbagen.2009.07.003
172. Campo GM, Avenoso A, Campo S, D'Ascola A, Nastasi G, Calatroni A. Molecular size hyaluronan differently modulates toll-like receptor-4 in LPS-induced inflammation in mouse chondrocytes. Biochimie (2010) 92:204-15. doi:10.1016/j.biochi.2009.10.006
173. Kashima Y, Takahashi M, Shiba Y, Itano N, Izawa A, Koyama J, et al. Crucial role of hyaluronan in neointimal formation after vascular injury. PLoS One (2013) 8:e58760. doi:10.1371/journal.pone.0058760
174. Rockey DC, Chung JJ, McKee CM, Noble PW. Stimulation of inducible nitric oxide synthase in rat liver by hyaluronan fragments. Hepatology (1998) 27:86-92. doi:10.1002/hep.510270115
175. Kothapalli D, Flowers J, Xu T, Puré E, Assoian RK. Differential activation of ERK and Rac mediates the proliferative and anti-proliferative effects of hyaluronan and CD44. J Biol Chem (2008) 283:31823-9. doi:10.1074/jbc. M802934200
176. Zhao H, Leu S-W, Shi L, Dedaj R, Zhao G, Garg HG, et al. TLR4 is a negative regulator in noninfectious lung inflammation. J Immunol (2010) 184:5308-14. doi:10.4049/jimmunol.1000009
177. Ke C, Wang D, Sun Y, Qiao D, Ye H, Zeng X. Immunostimulatory and antiangiogenic activities of low molecular weight hyaluronic acid. Food Chem Toxicol (2013) 58:401-7. doi:10.1016/j.fct.2013.05.032
178. Thaete LG, Qu X-W, Jilling T, Crawford SE, Fitchev P, Hirsch E, et al. Impact of toll-like receptor 4 deficiency on the response to uterine ischemia/reperfusion in mice. Reproduction (2013) 145:517-26. doi:10.1530/REP-12-0433
179. Kouvidi K, Berdiaki A, Nikitovic D, Katonis P, Afratis N, Hascall VC, et al. Role of receptor for hyaluronic acid-mediated motility (RHAMM) in low molecular weight hyaluronan (LMWHA)-mediated fibrosarcoma cell adhesion. J Biol Chem (2011) 286:38509-20. doi:10.1074/jbc. M111.275875
180. Tofuku K, Yokouchi M, Murayama T, Minami S, Komiya S. HAS3-related hyaluronan enhances biological activities necessary for metastasis of osteosarcoma cells. Int J Oncol (2006) 29:175-83. doi:10.3892/ijo.29.1.1.175
181. Fitzgerald KA, Bowie AG, Skeffington BS, O'Neill LA. Ras, protein kinase C zeta, and I kappa B kinases 1 and 2 are downstream effectors of CD44 during the activation of NF-kappa B by hyaluronic acid fragments in T-24 carcinoma cells. J Immunol (2000) 164:2053-63. doi:10.4049/jimmunol.164.4.2053
182. Yang T, Witham TF, Villa L, Erff M, Attanucci J, Watkins S, et al. Glioma-associated hyaluronan induces apoptosis in dendritic cells via inducible nitric oxide synthase: implications for the use of dendritic cells for therapy of gliomas. Cancer Res (2002) 62:2583-91.
183. Alaniz L, Rizzo M, Malvicini M, Jaunarena J, Avella D, Atorrasagasti C, et al. Low molecular weight hyaluronan inhibits colorectal carcinoma growth by decreasing tumor cell proliferation and stimulating immune response. Cancer Lett (2009) 278:9-16. doi:10.1016/j.canlet.2008.12.029
184. Alaniz L, Rizzo M, Garcia MG, Piccioni F, Aquino JB, Malvicini M, et al. Low molecular weight hyaluronan preconditioning of tumor-pulsed dendritic cells increases their migratory ability and induces immunity against murine colorectal carcinoma. Cancer Immunol Immunother (2011) 60:1383-95. doi:10.1007/s00262-011-1036-0
185. Cichy J, Puré E. The liberation of CD44. J Cell Biol (2003) 161:839-43. doi:10.1083/jcb.200302098
186. Cichy J, Kulig P, Puré E. Regulation of the release and function of tumor cell-derived soluble CD44. Biochim Biophys Acta (2005) 1745:59-64. doi:10.1016/j.bbamcr.2005.02.006
187. Lesley J, Hyman R, Kincade PW. CD44 and its interaction with extracellular matrix. Adv Immunol (1993) 54:271-335. doi:10.1016/S0065-2776(08)60537-4
188. Camp RL, Kraus TA, Puré E. Variations in the cytoskeletal interaction and posttranslational modification of the CD44 homing receptor in macrophages. J Cell Biol (1991) 115:1283-92. doi:10.1083/jcb.115.5.1283
189. Jiang H, Peterson RS, Wang W, Bartnik E, Knudson CB, Knudson W. A requirement for the CD44 cytoplasmic domain for hyaluronan binding, pericellular matrix assembly, and receptor-mediated endocytosis in COS-7 cells. J Biol Chem (2002) 277:10531-8. doi:10.1074/jbc. M108654200
190. Puré E, Camp RL, Peritt D, Panettieri RA, Lazaar AL, Nayak S. Defective phosphorylation and hyaluronate binding of CD44 with point mutations in the cytoplasmic domain. J Exp Med (1995) 181:55-62. doi:10.1084/jem.181.1.55
191. Katoh S, Zheng Z, Oritani K, Shimozato T, Kincade PW. Glycosylation of CD44 negatively regulates its recognition of hyaluronan. J Exp Med (1995) 182:419-29. doi:10.1084/jem.182.2.419
192. Gasbarri A, Del Prete F, Girnita L, Martegani MP, Natali PG, Bartolazzi A. CD44s adhesive function spontaneous and PMA-inducible CD44 cleavage are regulated at post-translational level in cells of melanocytic lineage. Melanoma Res (2003) 13:325-37. doi:10.1097/01.cmr.0000056256.56735.0f
193. Ruffell B, Poon GFT, Lee SSM, Brown KL, Tjew S-L, Cooper J, et al. Differential use of chondroitin sulfate to regulate hyaluronan binding by receptor CD44 in inflammatory and interleukin 4-activated macrophages. J Biol Chem (2011) 286:19179-90. doi:10.1074/jbc. M110.200790
194. Schmits R, Filmus J, Gerwin N, Senaldi G, Kiefer F, Kundig T, et al. CD44 regulates hematopoietic progenitor distribution, granuloma formation, and tumorigenicity. Blood (1997) 90:2217-33.
195. Teder P, Vandivier RW, Jiang D, Liang J, Cohn L, Puré E, et al. Resolution of lung inflammation by CD44. Science (2002) 296:155-8. doi:10.1126/science.1069659
196. Cuff CA, Kothapalli D, Azonobi I, Chun S, Zhang Y, Belkin R, et al. The adhesion receptor CD44 promotes atherosclerosis by mediating inflammatory cell recruitment and vascular cell activation. J Clin Invest (2001) 108:1031-40. doi:10.1172/JCI12455
197. Zhao L, Lee E, Zukas AM, Middleton MK, Kinder M, Acharya PS, et al. CD44 expressed on both bone marrow-derived and non-bone marrow-derived cells promotes atherogenesis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol (2008) 28:1283-9. doi:10.1161/ATVBAHA.108.165753
198. Zhao L, Hall JA, Levenkova N, Lee E, Middleton MK, Zukas AM, et al. CD44 regulates vascular gene expression in a proatherogenic environment. Arterioscler Thromb Vasc Biol (2007) 27:886-92. doi:10.1161/01.ATV.0000259362.10882.c5
199. Nandi A, Estess P, Siegelman MH. Hyaluronan anchoring and regulation on the surface of vascular endothelial cells is mediated through the functionally active form of CD44. J Biol Chem (2000) 275:14939-48. doi:10.1074/jbc.275.20.14939
200. Johnson P, Maiti A, Brown KL, Li R. A role for the cell adhesion molecule CD44 and sulfation in leukocyte-endothelial cell adhesion during an inflammatory response? Biochem Pharmacol (2000) 59:455-65. doi:10.1016/S0006-2952(99)00266-X
201. Mummert ME. Immunologic roles of hyaluronan. Immunol Res (2005) 31:189-206. doi:10.1385/IR:31:3:189
202. Mummert ME, Mohamadzadeh M, Mummert DI, Mizumoto N, Takashima A. Development of a peptide inhibitor of hyaluronan-mediated leukocyte trafficking. J Exp Med (2000) 192:769-79. doi:10.1084/jem.192.6.769
203. Singleton PA, Salgia R, Moreno-Vinasco L, Moitra J, Sammani S, Mirzapoiazova T, et al. CD44 regulates hepatocyte growth factor-mediated vascular integrity. Role of c-Met, Tiam1/Rac1, dynamin 2, and cortactin. J Biol Chem (2007) 282:30643-57. doi:10.1074/jbc. M702573200
204. Singleton PA, Mirzapoiazova T, Guo Y, Sammani S, Mambetsariev N, Lennon FE, et al. High-molecular-weight hyaluronan is a novel inhibitor of pulmonary vascular leakiness. Am J Physiol Lung Cell Mol Physiol (2010) 299:L639-51. doi:10.1152/ajplung.00405.2009
205. Harada N, Mizoi T, Kinouchi M, Hoshi K, Ishii S, Shiiba K, et al. Introduction of antisense CD44S CDNA down-regulates expression of overall CD44 isoforms and inhibits tumor growth and metastasis in highly metastatic colon carcinoma cells. Int J Cancer (2001) 91:67-75. doi:10.1002/1097-0215(20010101)91:1<67::AID-IJC1011>3.0.CO;2-D
206. Mummert ME, Mummert DI, Ellinger L, Takashima A. Functional roles of hyaluronan in B16-F10 melanoma growth and experimental metastasis in mice. Mol Cancer Ther (2003) 2:295-300.
207. Godar S, Ince TA, Bell GW, Feldser D, Donaher JL, Bergh J, et al. Growth-inhibitory and tumor-suppressive functions of p53 depend on its repression of CD44 expression. Cell (2008) 134:62-73. doi:10.1016/j.cell.2008.06.006
208. Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol (2008) 10:202-10. doi:10.1038/ncb1681
209. Afify A, Purnell P, Nguyen L. Role of CD44s and CD44v6 on human breast cancer cell adhesion, migration, and invasion. Exp Mol Pathol (2009) 86:95-100. doi:10.1016/j.yexmp.2008.12.003
210. Yang C, Cao M, Liu H, He Y, Xu J, Du Y, et al. The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering. J Biol Chem (2012) 287:43094-107. doi:10.1074/jbc. M112.349209
211. Qhattal HSS, Liu X. Characterization of CD44-mediated cancer cell uptake and intracellular distribution of hyaluronan-grafted liposomes. Mol Pharm (2011) 8:1233-46. doi:10.1021/mp2000428
212. Pusch A, Boeckenhoff A, Glaser T, Kaminski T, Kirfel G, Hans M, et al. CD44 and hyaluronan promote invasive growth of B35 neuroblastoma cells into the brain. Biochim Biophys Acta (2010) 1803:261-74. doi:10.1016/j.bbamcr.2009.12.003
213. Sugahara KN, Hirata T, Tanaka T, Ogino S, Takeda M, Terasawa H, et al. Chondroitin sulfate E fragments enhance CD44 cleavage and CD44-dependent motility in tumor cells. Cancer Res (2008) 68:7191-9. doi:10.1158/0008-5472.CAN-07-6198
214. Rutnam ZJ, Yang BB. The non-coding 3' UTR of CD44 induces metastasis by regulating extracellular matrix functions. J Cell Sci (2012) 125:2075-85. doi:10.1242/jcs100818
215. Huebener P, Abou-Khamis T, Zymek P, Bujak M, Ying X, Chatila K, et al. CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. J Immunol (2008) 180:2625-33. doi:10.4049/jimmunol.180.4.2625
216. Müller J, Gorressen S, Grandoch M, Feldmann K, Kretschmer I, Lehr S, et al. Interleukin-6-dependent phenotypic modulation of cardiac fibroblasts after acute myocardial infarction. Basic Res Cardiol (2014) 109:440. doi:10.1007/s00395-014-0440-y
217. Acharya PS, Majumdar S, Jacob M, Hayden J, Mrass P, Weninger W, et al. Fibroblast migration is mediated by CD44-dependent TGF beta activation. J Cell Sci (2008) 121:1393-402. doi:10.1242/jcs.021683
218. Tolg C, Hamilton SR, Nakrieko K-A, Kooshesh F, Walton P, McCarthy JB, et al. Rhamm-/-fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair. J Cell Biol (2006) 175:1017-28. doi:10.1083/jcb.200511027
219. Wolny PM, Banerji S, Gounou C, Brisson AR, Day AJ, Jackson DG, et al. Analysis of CD44-hyaluronan interactions in an artificial membrane system: insights into the distinct binding properties of high and low molecular weight hyaluronan. J Biol Chem (2010) 285:30170-80. doi:10.1074/jbc. M110.137562
220. Haserodt S, Aytekin M, Dweik RA. A comparison of the sensitivity, specificity, and molecular weight accuracy of three different commercially available hyaluronan ELISA-like assays. Glycobiology (2011) 21:175-83. doi:10.1093/glycob/cwq145
221. Skandalis SS, Stylianou M, Vynios DH, Papageorgakopoulou N, Theocharis DA. The structural and compositional changes of glycosaminoglycans are closely associated with tissue type in human laryngeal cancer. Biochimie (2007) 89:1573-80. doi:10.1016/j.biochi.2007.07.006
222. Hampson IN, Gallagher JT. Separation of radiolabelled glycosaminoglycan oligosaccharides by polyacrylamide-gel electrophoresis. Biochem J (1984) 221:697-705.
223. Bhilocha S, Amin R, Pandya M, Yuan H, Tank M, LoBello J, et al. Agarose and polyacrylamide gel electrophoresis methods for molecular mass analysis of 5-to 500-kDa hyaluronan. Anal Biochem (2011) 417:41-9. doi:10.1016/j.ab.2011.05.026
224. Cowman MK, Chen CC, Pandya M, Yuan H, Ramkishun D, LoBello J, et al. Improved agarose gel electrophoresis method and molecular mass calculation for high molecular mass hyaluronan. Anal Biochem (2011) 417:50-6. doi:10.1016/j.ab.2011.05.023
225. Kamada H, Masuda K, D'Souza AL, Lenz ME, Pietryla D, Otten L, et al. Age-related differences in the accumulation and size of hyaluronan in alginate culture. Arch Biochem Biophys (2002) 408:192-9. doi:10.1016/S0003-9861(02)00543-X
226. Lee HG, Cowman MK. An agarose gel electrophoretic method for analysis of hyaluronan molecular weight distribution. Anal Biochem (1994) 219:278-87. doi:10.1006/abio.1994.1267
227. Lauer ME, Mukhopadhyay D, Fulop C, de la Motte CA, Majors AK, Hascall VC. Primary murine airway smooth muscle cells exposed to poly(I, C) or tunicamycin synthesize a leukocyte-adhesive hyaluronan matrix. J Biol Chem (2009) 284:5299-312. doi:10.1074/jbc. M807965200
228. Malm L, Hellman U, Larsson G. Size determination of hyaluronan using a gas-phase electrophoretic mobility molecular analysis. Glycobiology (2012) 22:7-11. doi:10.1093/glycob/cwr096
229. Hellman U, Malm L, Ma L-P, Larsson G, Mörner S, Fu M, et al. Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the extracellular matrix component hyaluronan. PLoS One (2010) 5:e14393. doi:10.1371/journal.pone.0014393
230. Kang DY, Kim W-S, Heo IS, Park YH, Lee S. Extraction of hyaluronic acid (HA) from rooster comb and characterization using flow field-flow fractionation (FlFFF) coupled with multiangle light scattering (MALS). J Sep Sci (2010) 33:3530-6. doi:10.1002/jssc.201000478
231. DeAngelis PL. Monodisperse hyaluronan polymers: synthesis and potential applications. Curr Pharm Biotechnol (2008) 9:246-8. doi:10.2174/138920108785161550
232. Boeriu CG, Springer J, Kooy FK, van den Broek LAM, Eggink G. Production methods for hyaluronan. Int J Carbohydr Chem (2013) 2013:14. doi:10.1155/9160
233. Marcellin E, Steen JA, Nielsen LK. Insight into hyaluronic acid molecular weight control. Appl Microbiol Biotechnol (2014) 98:6947-56. doi:10.1007/s00253-014-5853-x
234. Iannitti T, Lodi D, Palmieri B. Intra-articular injections for the treatment of osteoarthritis: focus on the clinical use of hyaluronic acid. Drugs R D (2011) 11:13-27. doi:10.2165/11539760-000000000-00000
235. Estes JM, Adzick NS, Harrison MR, Longaker MT, Stern R. Hyaluronate metabolism undergoes an ontogenic transition during fetal development: implications for scar-free wound healing. J Pediatr Surg (1993) 28:1227-31. doi:10.1016/S0022-3468(05)80303-3
236. Armstrong SE, Bell DR. Measurement of high-molecular-weight hyaluronan in solid tissue using agarose gel electrophoresis. Anal Biochem (2002) 308:255-64. doi:10.1016/S0003-2697(02)00239-7
237. Meyer FA, Preston BN, Lowther DA. Isolation and properties of hyaluronic acid from bovine heart valves. Biochem J (1969) 113:559-63.
238. Radhakrishnamurthy B, Dalferes ER, Vijayagopal P, Berenson GS. Determination of mulecular-weight distribution of aorta glycosaminoglycans by automated gel filtration. J Chromatogr (1980) 192:307-14. doi:10.1016/S0021-9673(80)80005-7
239. Chajara A, Raoudi M, Delpech B, Levesque H. The fibroproliferative response of arterial smooth muscle cells to balloon catheter injury is associated with increased hyaluronidase production and hyaluronan degradation. Atherosclerosis (2001) 157:293-300. doi:10.1016/S0021-9150(00)00727-9
240. Hamilton SR, Veiseh M, Tölg C, Tirona R, Richardson J, Brown R, et al. Pharmacokinetics and pharmacodynamics of hyaluronan infused into healthy human volunteers. Open Drug Metab J (2009) 3:43-55. doi:10.2174/1874073100903010043
241. Gustafson S. The influence of sulfated polysaccharides on the circulating levels of hyaluronan. Glycobiology (1997) 7:1209-14. doi:10.1093/glycob/7.8.1209
242. Sallisalmi M, Tenhunen J, Kultti A, Tammi M, Pettilä V. Plasma hyaluronan and hemorheology in patients with septic shock: a clinical and experimental study. Clin Hemorheol Microcirc (2014) 56:133-44. doi:10.3233/CH-131677
243. Tengblad A, Laurent UB, Lilja K, Cahill RN, Engström-Laurent A, Fraser JR, et al. Concentration and relative molecular mass of hyaluronate in lymph and blood. Biochem J (1986) 236:521-5.
244. Sasaki Y, Uzuki M, Nohmi K, Kitagawa H, Kamataki A, Komagamine M, et al. Quantitative measurement of serum hyaluronic acid molecular weight in rheumatoid arthritis patients and the role of hyaluronidase. Int J Rheum Dis (2011) 14:313-9. doi:10.1111/j.1756-185X.2011.01683.x
245. Murawaki Y, Ikuta Y, Idobe Y, Koda M, Kawasaki H. Molecular weight of hyaluronate in the serum of patients with chronic liver disease. Res Commun Mol Pathol Pharmacol (1998) 99:207-16.
246. Armstrong SE, Bell DR. Ischemia-reperfusion does not cause significant hyaluronan depolymerization in skeletal muscle. Microvasc Res (2002) 64:353-62. doi:10.1006/mvre.2002.2437
247. Laurent UB, Laurent TC, Hellsing LK, Persson L, Hartman M, Lilja K. Hyaluronan in human cerebrospinal fluid. Acta Neurol Scand (1996) 94:194-206. doi:10.1111/j.1600-0404.1996.tb07052.x
248. Bugiani M, Postma N, Polder E, Dieleman N, Scheffer PG, Sim FJ, et al. Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease. Brain (2013) 136:209-22. doi:10.1093/brain/aws320
249. Theocharis DA, Skandalis SS, Noulas AV, Papageorgakopoulou N, Theocharis AD, Karamanos NK. Hyaluronan and chondroitin sulfate proteoglycans in the supramolecular organization of the mammalian vitreous body. Connect Tissue Res (2008) 49:124-8. doi:10.1080/03008200802148496
250. Østerholt HCD, Dannevig I, Wyckoff MH, Liao J, Akgul Y, Ramgopal M, et al. Antioxidant protects against increases in low molecular weight hyaluronan and inflammation in asphyxiated newborn pigs resuscitated with 100% oxygen. PLoS One (2012) 7:e38839. doi:10.1371/journal.pone.0038839
251. Cheng G, Swaidani S, Sharma M, Lauer ME, Hascall VC, Aronica MA. Correlation of hyaluronan deposition with infiltration of eosinophils and lymphocytes in a cockroach-induced murine model of asthma. Glycobiology (2013) 23:43-58. doi:10.1093/glycob/cws122
252. Zelko IN, Folz RJ. Extracellular superoxide dismutase attenuates release of pulmonary hyaluronan from the extracellular matrix following bleomycin exposure. FEBS Lett (2010) 584:2947-52. doi:10.1016/j.febslet.2010.05.025
253. Mascarenhas MM, Day RM, Ochoa CD, Choi W-I, Yu L, Ouyang B, et al. Low molecular weight hyaluronan from stretched lung enhances interleukin-8 expression. Am J Respir Cell Mol Biol (2004) 30:51-60. doi:10.1165/rcmb.2002-0167OC
254. Nettelbladt O, Tengblad A, Hällgren R. Lung accumulation of hyaluronan parallels pulmonary edema in experimental alveolitis. Am J Physiol (1989) 257:L379-84.
255. Motomiya M, Endo M, Arai H, Yokosawa A, Sato H, Konno K. Biochemical characterization of hyaluronic acid from a case of benign, localized, pleural mesothelioma. Am Rev Respir Dis (1975) 111:775-80.
256. Tammi R, Säämänen AM, Maibach HI, Tammi M. Degradation of newly synthesized high molecular mass hyaluronan in the epidermal and dermal compartments of human skin in organ culture. J Invest Dermatol (1991) 97:126-30. doi:10.1111/1523-1747.ep12478553
257. Sakai S, Yasuda R, Sayo T, Ishikawa O, Inoue S. Hyaluronan exists in the normal stratum corneum. J Invest Dermatol (2000) 114:1184-7. doi:10.1046/j.1523-1747.2000.00992.x
258. Motohashi N, Nakamichi Y, Mori I, Nishikawa H, Umemoto J. Analysis by high-performance gel permeation chromatography of hyaluronic acid in animal skins and rabbit synovial fluid. J Chromatogr (1988) 435:335-42. doi:10.1016/S0021-9673(01)82193-2
259. Miyamoto I, Nagase S. Purification and characterization of hyaluronic acid from the horny layer of guinea pigs. J Biochem (1984) 95:1331-6.
260. Reed RK, Lilja K, Laurent TC. Hyaluronan in the rat with special reference to the skin. Acta Physiol Scand (1988) 134:405-11. doi:10.1111/j.1748-1716.1988.tb08508.x
261. Shimada E, Matsumura G. Molecular weight of hyaluronic acid from rabbit skin. J Biochem (1977) 81:79-91.
262. Dechert TA, Ducale AE, Ward SI, Yager DR. Hyaluronan in human acute and chronic dermal wounds. Wound Repair Regen (2006) 14:252-8. doi:10.1111/j.1743-6109.2006.00119.x
263. Reed MJ, Damodarasamy M, Chan CK, Johnson MNR, Wight TN, Vernon RB. Cleavage of hyaluronan is impaired in aged dermal wounds. Matrix Biol (2013) 32:45-51. doi:10.1016/j.matbio.2012.09.004
264. West DC, Shaw DM, Lorenz P, Adzick NS, Longaker MT. Fibrotic healing of adult and late gestation fetal wounds correlates with increased hyaluronidase activity and removal of hyaluronan. Int J Biochem Cell Biol (1997) 29:201-10. doi:10.1016/S1357-2725(96)00133-1
265. Miyamoto I, Nagase S. Age-related changes in the molecular weight of hyaluronic acid from rat skin. Jikken Dobutsu (1984) 33:481-5.
266. Tobiishi M, Sayo T, Yoshida H, Kusaka A, Kawabata K, Sugiyama Y, et al. Changes in epidermal hyaluronan metabolism following UVB irradiation. J Dermatol Sci (2011) 64:31-8. doi:10.1016/j.jdermsci.2011.06.006
267. Dahl LB, Dahl IM, Børresen AL. The molecular weight of sodium hyaluronate in amniotic fluid. Biochem Med Metab Biol (1986) 35:219-26. doi:10.1016/0885-4505(86)90077-0
268. Perry K, Haresign W, Wathes DC, Khalid M. Hyaluronan (HA) content, the ratio of HA fragments and the expression of CD44 in the ovine cervix vary with the stage of the oestrous cycle. Reproduction (2010) 140:133-41. doi:10.1530/REP-09-0424
269. Akgul Y, Holt R, Mummert M, Word A, Mahendroo M. Dynamic changes in cervical glycosaminoglycan composition during normal pregnancy and preterm birth. Endocrinology (2012) 153:3493-503. doi:10.1210/en.2011-1950
270. Ruscheinsky M, De la Motte C, Mahendroo M. Hyaluronan and its binding proteins during cervical ripening and parturition: dynamic changes in size, distribution and temporal sequence. Matrix Biol (2008) 27:487-97. doi:10.1016/j.matbio.2008.01.010
271. Cordo-Russo R, Garcia MG, Barrientos G, Orsal AS, Viola M, Moschansky P, et al. Murine abortion is associated with enhanced hyaluronan expression and abnormal localization at the fetomaternal interface. Placenta (2009) 30:88-95. doi:10.1016/j.placenta.2008.10.013
272. Goulas A, Hatzichristou DG, Karakiulakis G, Mirtsou-Fidani V, Kalinderis A, Papakonstantinou E. Benign hyperplasia of the human prostate is associated with tissue enrichment in chondroitin sulphate of wide size distribution. Prostate (2000) 44:104-10. doi:10.1002/1097-0045(20000701)44:2<104::AID-PROS2>3.0.CO;2-6
273. Lokeshwar VB, Rubinowicz D, Schroeder GL, Forgacs E, Minna JD, Block NL, et al. Stromal and epithelial expression of tumor markers hyaluronic acid and HYAL1 hyaluronidase in prostate cancer. J Biol Chem (2001) 276:11922-32. doi:10.1074/jbc. M008432200
274. Ng CK, Handley CJ, Preston BN, Robinson HC. The extracellular processing and catabolism of hyaluronan in cultured adult articular cartilage explants. Arch Biochem Biophys (1992) 298:70-9. doi:10.1016/0003-9861(92)90095-E
275. Sztrolovics R, Recklies AD, Roughley PJ, Mort JS. Hyaluronate degradation as an alternative mechanism for proteoglycan release from cartilage during interleukin-1beta-stimulated catabolism. Biochem J (2002) 362:473-9. doi:10.1042/0264-6021:3620473
276. Holmes MW, Bayliss MT, Muir H. Hyaluronic acid in human articular cartilage. Age-related changes in content and size. Biochem J (1988) 250:435-41.
277. Coleman PJ, Scott D, Ray J, Mason RM, Levick JR. Hyaluronan secretion into the synovial cavity of rabbit knees and comparison with albumin turnover. J Physiol (1997) 503(Pt 3):645-56. doi:10.1111/j.1469-7793.1997.645bg.x
278. Tulamo RM, Heiskanen T, Salonen M. Concentration and molecular weight distribution of hyaluronate in synovial fluid from clinically normal horses and horses with diseased joints. Am J Vet Res (1994) 55:710-5.
279. Band PA, Heeter J, Wisniewski H-G, Liublinska V, Pattanayak CW, Karia RJ, et al. Hyaluronan molecular weight distribution is associated with the risk of knee osteoarthritis progression. Osteoarthritis Cartilage (2014) 23:70-6. doi:10.1016/j.joca.2014.09.017
280. Barton KI, Ludwig TE, Achari Y, Shrive NG, Frank CB, Schmidt TA. Characterization of proteoglycan 4 and hyaluronan composition and lubrication function of ovine synovial fluid following knee surgery. J Orthop Res (2013) 31:1549-54. doi:10.1002/jor.22399
281. Wei L, Xiong H, Li B, Gong Z, Li J, Cai H, et al. Change of HA molecular size and boundary lubrication in synovial fluid of patients with temporomandibular disorders. J Oral Rehabil (2010) 37:271-7. doi:10.1111/j.1365-2842.2009.02048.x
282. Schenck P, Schneider S, Miehlke R, Prehm P. Synthesis and degradation of hyaluronate by synovia from patients with rheumatoid arthritis. J Rheumatol (1995) 22:400-5.
283. Vasan NS, Saporito RA, Saraswathi S, Tesoriero JV, Manley S. Alterations of renal cortex and medullary glycosaminoglycans in aging dog kidney. Biochim Biophys Acta (1983) 760:197-205. doi:10.1016/0304-4165(83)90164-2
284. Declèves A-E, Caron N, Voisin V, Legrand A, Bouby N, Kultti A, et al. Synthesis and fragmentation of hyaluronan in renal ischaemia. Nephrol Dial Transplant (2012) 27:3771-81. doi:10.1093/ndt/gfs098
285. Lokeshwar VB, Obek C, Soloway MS, Block NL. Tumor-associated hyaluronic acid: a new sensitive and specific urine marker for bladder cancer. Cancer Res (1997) 57:773-7.
286. Purvis JA, Embery G, Oliver WM. Molecular size distribution of proteoglycans in human inflamed gingival tissue. Arch Oral Biol (1984) 29:513-9. doi:10.1016/0003-9969(84)90072-4
287. Schmaus A, Klusmeier S, Rothley M, Dimmler A, Sipos B, Faller G, et al. Accumulation of small hyaluronan oligosaccharides in tumour interstitial fluid correlates with lymphatic invasion and lymph node metastasis. Br J Cancer (2014) 111:559-67. doi:10.1038/bjc.2014.332
288. Lv H, Yu G, Sun L, Zhang Z, Zhao X, Chai W. Elevate level of glycosaminoglycans and altered sulfation pattern of chondroitin sulfate are associated with differentiation status and histological type of human primary hepatic carcinoma. Oncology (2007) 72:347-56. doi:10.1159/000113145
289. Kittlick PD, Engelmann D. The glycosaminoglycans in cultures of stimulated rat peritoneal macrophages. 2. Gel chromatographic studies and the behaviour of heparan sulfate. Exp Toxicol Pathol (1993) 45:87-92. doi:10.1016/S0940-2993(11)80469-0