Inhibition of hyaluronan synthase 2 reduces the abnormal migration rate of keloid keratinocytes

Journal of Burn Care and Research

Volumn 35, Issue 1, 2014, Pages 84-92

  Supp, Dorothy M ^a,b   Hahn, Jennifer M ^a   McFarland, Kevin L ^a   Glaser, Kathryn ^a  

^a SHRINERS HOSPITALS FOR CHILDREN   (United States)

^b UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HYALURONAN SYNTHASE 1; HYALURONAN SYNTHASE 2; HYALURONAN SYNTHASE 3; HYMECROMONE; SYNTHETASE; UNCLASSIFIED DRUG;

ADULT; ARTICLE; ASSAY; CELL MIGRATION; CHILD; CHROMOSOME ABERRATION; CONTROLLED STUDY; ENZYME INHIBITION; ENZYME SYNTHESIS; FEMALE; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VITRO STUDY; KELOID; KERATINOCYTE; MALE; PHENOTYPE; PRESCHOOL CHILD; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; SCAR FORMATION; SCHOOL CHILD; SKIN; WOUND; YOUNG ADULT;

ADOLESCENT; ADULT; CELL MOVEMENT; CELL PROLIFERATION; CHILD; CHILD, PRESCHOOL; FEMALE; GLUCURONOSYLTRANSFERASE; HUMANS; HYMECROMONE; INDICATORS AND REAGENTS; KELOID; KERATINOCYTES; MALE; PHENOTYPE; REAL-TIME POLYMERASE CHAIN REACTION; RNA;

EID: 84892805020     PISSN: 1559047X     EISSN: 15590488     Source Type: Journal    
DOI: 10.1097/BCR.0b013e3182a2a9dd     Document Type: Article

References (65)

1. Juckett G, Hartman-Adams H. Management of keloids and hypertrophic scars. Am Fam Physician 2009;80:253-60.
2. Gauglitz GG, Korting HC, Pavicic T, Ruzicka T, Jeschke MG. Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med 2011;17:113-25.
3. Bock O, Schmid-Ott G, Malewski P, Mrowietz U. Quality of life of patients with keloid and hypertrophic scarring. Arch Dermatol Res 2006;297:433-8.
4. Balci DD, Inandi T, Dogramaci CA, Celik E. DLQI scores in patients with keloids and hypertrophic scars: a prospective case control study. J Dtsch Dermatol Ges 2009;7:688-92.
5. Chike-Obi CJ, Cole PD, Brissett AE. Keloids: pathogenesis, clinical features, and management. Semin Plast Surg 2009;23:178-84.
6. Clark JA, Turner ML, Howard L, Stanescu H, Kleta R, Kopp JB. Description of familial keloids in five pedigrees: evidence for autosomal dominant inheritance and phenotypic heterogeneity. BMC Dermatol 2009;9:8.
7. Marneros AG, Norris JE, Olsen BR, Reichenberger E. Clinical genetics of familial keloids. Arch Dermatol 2001;137:1429-34.
8. Marneros AG, Norris JE, Watanabe S, Reichenberger E, Olsen BR. Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23 and 7p11. J Invest Dermatol 2004;122:1126-32.
9. Shih B, Bayat A. Genetics of keloid scarring. Arch Dermatol Res 2010;302:319-39.
10. Halim AS, Emami A, Salahshourifar I, Kannan TP. Keloid scarring: understanding the genetic basis, advances, and prospects. Arch Plast Surg 2012;39:184-9.
11. Brown JJ, Bayat A. Genetic susceptibility to raised dermal scarring. Br J Dermatol 2009;161:8-18.
12. Catherino WH, Leppert PC, Stenmark MH, et al. Reduced dermatopontin expression is a molecular link between uterine leiomyomas and keloids. Genes Chromosomes Cancer 2004;40:204-17.
13. Carrino DA, Mesiano S, Barker NM, Hurd WW, Caplan AI. Proteoglycans of uterine fibroids and keloid scars: similarity in their proteoglycan composition. Biochem J 2012;443:361-8.
14. Luo X, Pan Q, Liu L, Chegini N. Genomic and proteomic profiling II: comparative assessment of gene expression profiles in leiomyomas, keloids, and surgically-induced scars. Reprod Biol Endocrinol 2007;5:35.
15. Leppert PC, Catherino WH, Segars JH. A new hypothesis about the origin of uterine fibroids based on gene expression profiling with microarrays. Am J Obstet Gynecol 2006;195:415-20.
16. Eiser AR. Does over-expression of transforming growth factor-beta account for the increased morbidity in African-Americans?: possible clinical study and therapeutic implications. Med Hypotheses 2010;75:418-21.
17. Dustan HP. Does keloid pathogenesis hold the key to understanding black/white differences in hypertension severity? Hypertension 1995;26(6 Pt 1):858-62.
18. Patel PA, Bailey JK, Yakuboff KP. Treatment outcomes for keloid scar management in the pediatric burn population. Burns 2012;38:767-71.
19. Durani P, Bayat A. Levels of evidence for the treatment of keloid disease. J Plast Reconstr Aesthet Surg 2008;61:4-17.
20. Shih B, Garside E, McGrouther DA, Bayat A. Molecular dissection of abnormal wound healing processes resulting in keloid disease. Wound Repair Regen 2010;18:139-53.
21. Boyce DE, Ciampolini J, Ruge F, Murison MS, Harding KG. Inflammatory-cell subpopulations in keloid scars. Br J Plast Surg 2001;54:511-6.
22. Lim IJ, Phan TT, Song C, Tan WT, Longaker MT. Investigation of the influence of keloid-derived keratinocytes on fibroblast growth and proliferation in vitro. Plast Reconstr Surg 2001;107:797-808.
23. Funayama E, Chodon T, Oyama A, Sugihara T. Keratinocytes promote proliferation and inhibit apoptosis of the underlying fibroblasts: an important role in the pathogenesis of keloid. J Invest Dermatol 2003;121:1326-31.
24. Lim IJ, Phan TT, Bay BH, et al. Fibroblasts cocultured with keloid keratinocytes: normal fibroblasts secrete collagen in a keloidlike manner. Am J Physiol Cell Physiol 2002;283:C212-22.
25. Phan TT, Lim IJ, Bay BH, et al. Differences in collagen production between normal and keloid-derived fibroblasts in serum-media co-culture with keloid-derived keratinocytes. J Dermatol Sci 2002;29:26-34.
26. Lim CP, Phan TT, Lim IJ, Cao X. Cytokine profiling and Stat3 phosphorylation in epithelial-mesenchymal interactions between keloid keratinocytes and fibroblasts. J Invest Dermatol 2009;129:851-61.
27. Hahn JM, Glaser K, McFarland KL, Aronow BJ, Boyce ST, Supp DM. Keloid-derived keratinocytes exhibit an abnormal gene expression profile consistent with a distinct causal role in keloid pathology. Wound Repair Regen 2013;21:530-44.
28. Zeisberg M, Neilson EG. Biomarkers for epithelial-mesenchymal transitions. J Clin Invest 2009;119:1429-37.
29. Gröger CJ, Grubinger M, Waldhör T, Vierlinger K, Mikulits W. Meta-analysis of gene expression signatures defining the epithelial to mesenchymal transition during cancer progression. PLoS One 2012;7:e51136.
30. Jagadeesan J, Bayat A. Transforming growth factor beta (TGFbeta) and keloid disease. Int J Surg 2007;5:278-85.
31. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelialmesenchymal transitions in development and disease. Cell 2009;139:871-90.
32. Leopold PL, Vincent J, Wang H. A comparison of epithelialto-mesenchymal transition and re-epithelialization. Semin Cancer Biol 2012;22:471-83.
33. Mansbridge JN, Knapp AM. Changes in keratinocyte maturation during wound healing. J Invest Dermatol 1987;89:253-63.
34. Lee JM, Dedhar S, Kalluri R, Thompson EW. The epithelialmesenchymal transition: new insights in signaling, development, and disease. J Cell Biol 2006;172:973-81.
35. Butler PD, Longaker MT, Yang GP. Current progress in keloid research and treatment. J Am Coll Surg 2008;206:731-41.
36. Rilla K, Lammi MJ, Sironen R, et al. Changed lamellipodial extension, adhesion plaques and migration in epidermal keratinocytes containing constitutively expressed sense and antisense hyaluronan synthase 2 (Has2) genes. J Cell Sci 2002;115(Pt 18):3633-43.
37. Guo N, Li X, Mann MM, et al. Hyaluronan synthesis mediates the fibrotic response of keratinocytes to transforming growth factor beta. J Biol Chem 2010;285(42):32012-9.
38. Supp DM, Hahn JM, Glaser K, McFarland KL, Boyce ST. Deep and superficial keloid fibroblasts contribute differentially to tissue phenotype in a novel in vivo model of keloid scar. Plast Reconstr Surg 2012;129:1259-71.
39. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 2001;25:402-8.
40. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55-63.
41. Rilla K, Pasonen-Seppänen S, Rieppo J, Tammi M, Tammi R. The hyaluronan synthesis inhibitor 4-methylumbelliferone prevents keratinocyte activation and epidermal hyperproliferation induced by epidermal growth factor. J Invest Dermatol 2004;123:708-14.
42. Kultti A, Pasonen-Seppänen S, Jauhiainen M, et al. 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3. Exp Cell Res 2009;315:1914-23.
43. Itano N, Sawai T, Yoshida M, et al. Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem 1999;274:25085-92.
44. Adamia S, Maxwell CA, Pilarski LM. Hyaluronan and hyaluronan synthases: potential therapeutic targets in cancer. Curr Drug Targets Cardiovasc Haematol Disord 2005;5:3-14.
45. Hascall VC, Majors AK, De La Motte CA, et al. Intracellular hyaluronan: a new frontier for inflammation? Biochim Biophys Acta 2004;1673:3-12.
46. Noble PW. Hyaluronan and its catabolic products in tissue injury and repair. Matrix Biol 2002;21:25-9.
47. Meran S, Thomas D, Stephens P, et al. Involvement of hyaluronan in regulation of fibroblast phenotype. J Biol Chem 2007;282:25687-97.
48. 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.
49. Lokeshwar VB, Lopez LE, Munoz D, et al. Antitumor activity of hyaluronic acid synthesis inhibitor 4-methylumbelliferone in prostate cancer cells. Cancer Res 2010;70:2613-23.
50. Yoshihara S, Kon A, Kudo D, et al. A hyaluronan synthase suppressor, 4-methylumbelliferone, inhibits liver metastasis of melanoma cells. FEBS Lett 2005;579:2722-6.
51. Okuda H, Kobayashi A, Xia B, et al. Hyaluronan synthase HAS2 promotes tumor progression in bone by stimulating the interaction of breast cancer stem-like cells with macrophages and stromal cells. Cancer Res 2012;72:537-47.
52. Arai E, Nishida Y, Wasa J, et al. Inhibition of hyaluronan retention by 4-methylumbelliferone suppresses osteosarcoma cells in vitro and lung metastasis in vivo. Br J Cancer 2011;105:1839-49.
53. Saito T, Tamura D, Nakamura T, et al. 4-methylumbelliferone leads to growth arrest and apoptosis in canine mammary tumor cells. Oncol Rep 2013;29:335-42.
54. Li Y, Li L, Brown TJ, Heldin P. Silencing of hyaluronan synthase 2 suppresses the malignant phenotype of invasive breast cancer cells. Int J Cancer 2007;120:2557-67.
55. Udabage L, Brownlee GR, Nilsson SK, Brown TJ. The overexpression of HAS2, Hyal-2 and CD44 is implicated in the invasiveness of breast cancer. Exp Cell Res 2005;310:205-17.
56. Kosaki R, Watanabe K, Yamaguchi Y. Overproduction of hyaluronan by expression of the hyaluronan synthase Has2 enhances anchorage-independent growth and tumorigenicity. Cancer Res 1999;59:1141-5.
57. Camenisch TD, Spicer AP, Brehm-Gibson T, 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.
58. Zoltan-Jones A, Huang L, Ghatak S, Toole BP. Elevated hyaluronan production induces mesenchymal and transformed properties in epithelial cells. J Biol Chem 2003;278:45801-10.
59. Porsch H, Bernert B, Mehic M, et al. Efficient TGFbetainduced epithelial-mesenchymal transition depends on hyaluronan synthase HAS2. Oncogene 2012;10.
60. Meyer LJ, Russell SB, Russell JD, et al. Reduced hyaluronan in keloid tissue and cultured keloid fibroblasts. J Invest Dermatol 2000;114:953-9.
61. Tan KT, McGrouther DA, Day AJ, Milner CM, Bayat A. Characterization of hyaluronan and TSG-6 in skin scarring: differential distribution in keloid scars, normal scars and unscarred skin. J Eur Acad Dermatol Venereol 2011;25:317-27.
62. Benitez A, Yates TJ, Shamaldevi N, Bowen T, Lokeshwar VB. Dietary supplement hymecromone and sorafenib: a novel combination for the control of renal cell carcinoma. J Urol 2013;190:285-90.
63. Abate A, Dimartino V, Spina P, et al. Hymecromone in the treatment of motor disorders of the bile ducts: a multicenter, double-blind, placebo-controlled clinical study. Drugs Exp Clin Res 2001;27:223-31.
64. Piccioni F, Malvicini M, Garcia MG, et al. Antitumor effects of hyaluronic acid inhibitor 4-methylumbelliferone in an orthotopic hepatocellular carcinoma model in mice. Glycobiology 2012;22:400-10.
65. Yoshioka Y, Kozawa E, Urakawa H, et al. Suppression of hyaluronan synthesis alleviates inflammatory responses in murine arthritis and in human rheumatoid synovial fibroblasts. Arthritis Rheum 2013;65:1160-70.