The myofibroblast: Phenotypic characterization as a prerequisite to understanding its functions in translational medicine: Translational Medicine

Journal of Cellular and Molecular Medicine

Volumn 12, Issue 1, 2008, Pages 22-37

  Eyden, B ^a  

^a CHRISTIE HOSPITAL   (United Kingdom)

Author keywords

Cancer; Fibrosis; Myofibroblast; Stroma; Therapy; Tumour; Ultrastructure

Indexed keywords

EID: 41149107510     PISSN: 15821838     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1582-4934.2007.00213.x     Document Type: Article

References (117)

1. Gabbiani G, Ryan GB, Majno G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia. 1971 27 : 549 50.
2. Majno G, Gabbiani G, Hirschel BJ, Ryan GB, Statkov PR. Contraction of granulation tissue in vitro: similarity to smooth muscle. Science. 1971 173 : 548 50.
3. Seemayer TA, Lagacé R, Schürch W, Thelmo WL. The myofibroblast: biologic, pathologic, and theoretical considerations. Pathol Annu. 1980 15 : 443 70.
4. Lipper S, Kahn LB, Reddick RL. The myofibroblast. Pathol Annu. 1980 15 : 409 41.
5. nd edition, SS Sternberg (ed 1997, Lippincott, Raven, pp. 129 65.
6. Schürch W, Seemayer TA, Gabbiani G. The myofibroblast: a quarter century after its discovery. Am J Surg Pathol. 1998 22 : 141 7.
7. Gabbiani G. The myofibroblast in wound healing and fibrocontractive diseases. J Pathol. 2003 200 : 500 3.
8. 2-terminal peptide of α-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo. J Cell Biol. 2002 157 : 657 63.
9. Joyce JA. Therapeutic targeting of the tumor microenvironment. Cancer Cell. 2005 7 : 513 20.
10. Eyden BP. Brief review of the fibronexus and its significance for myofibroblastic differentiation and tumor diagnosis. Ultrastruct Pathol. 1993 17 : 611 22.
11. Eyden BP. The myofibroblast: an assessment of controversial issues and a definition useful in diagnosis and research. Ultrastruct Pathol. 2001 25 : 39 50.
12. Eyden BP. The fibronexus in reactive and tumoral myofibroblasts: further characterisation by electron microscopy. Histol Histopathol. 2001 16 : 57 70.
13. Eyden B. Electron microscopy in the study of myofibroblastic lesions. Sem Diagn Pathol. 2003 20 : 13 24.
14. Eyden B. The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. Part 1 - normal and reactive cells. J submicrosc Cytol Pathol. 2005 37 : 109 204.
15. Eyden B. The myofibroblast: a study of normal, reactive and neoplastic tissues with an emphasis on ultra-structure. Nuova Immagine Editrice, Siena, 2007.
16. Ryan GB, Cliff WJ, Gabbiani G, Irle C, Montandon D, Statkov PR, Majno G. Myofibroblasts in human granulation tissue. Hum Pathol. 1974 5 : 55 67.
17. Singer II, Kawka DW, Kazazis DM, Clark RAF. In vivo codistribution of fibronectin and actin fibers in granulation tissue. Immunofluorescence and electron microscope studies at the myofibroblast surface. J Cell Biol. 1984 98 : 2091 106.
18. Singer II, Kazazis DM, Kawka DW. Localization of the fibronexus at the surface of granulation tissue myofibroblasts using double-label immunogold electron microscopy on ultrathin frozen sections. Eur J Cell Biol. 1985 38 : 94 101.
19. Singer II. The fibronexus. A transmembrane association of fibronectin-containing fibers and bundles of 5 nm microfilaments in hamster and human fibroblasts. Cell. 1979 6 : 675 85.
20. Skalli O, Schürch W, Seemayer TA, Lagacé R, Montandon D, Pitter B, Gabbiani G. Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins. Lab Invest. 1989 60 : 275 85.
21. Jabs A, Moncada GA, Nichols CE, Waller EK, Wilcox JN. Peripheral blood mononuclear cells acquire myofibroblastic characteristics in granulation tissue. J Vasc Res. 2005 42 : 174 80.
22. Sharif-Afshar A-R, Donohoe JM, Pope JC, Adams MC, Brock III. JW, Bhowmick NA. Stromal hyperplasia in male bladders upon loss of transforming growth factor-β signalling in fibroblasts. J Urol. 2005 174 : 1704 7.
23. Orimo A, Weinberg RA. Stromal fibroblasts in cancer. Cell Cycle. 2006 5 : 1597 601.
24. Ono Y, Sensui H, Okutsu S, Nagatomi R. Notch2 negatively regulates myofibroblastic differentiation of myoblasts. J Cell Physiol. 2007 210 : 358 69.
25. Prakash S, Paul WE, Robbins PW. Fibrosin, a novel fibrogenic cytokine, modulates expression of myofibroblasts. Exp Mol Pathol. 2007 82 : 42 8.
26. Beranek JT. Alpha-smooth muscle actin is not a specific and, consequently, a reliable marker for smooth muscle cells. Hum Path. 1993 24 : 813 4.
27. Eyden BP. Smooth-muscle-type myofilaments and actin in reactive and neoplastic nonmuscle cells. Ultrastruct Pathol. 2000 24 : 347 52.
28. Truong LD, Rangdaeng S, Cagle P, Ro JY, Hawkins H, Font, RL. The diagnostic utility of desmin. A study of 584 cases and review of the literature. Am J Clin Pathol. 1990 93 : 305 14.
29. Eyden B. The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultra-structure. Part 2 - Tumours and tumour-like lesions. J Submicrosc Cytol Pathol. 2005 37 : 231 96.
30. Wiseman OJ, Fowler CJ, Landon DN. The role of human bladder lamina propria myofibroblast. BJU International. 2003 91 : 89 93.
31. Selmy GI, Hassouna MM, Bégin LR, Khaliof IM, Elhilali MM. Long-term effects of ureteric stent after ureteric dilation. J Urol. 1989 150 : 1984 9.
32. Schürch W, Skalli O, Gabbiani G. Cellular Biology. The myofibroblast. Definition, ultrastructural features and role in wound contraction (Chapter 4). In : Dupuytren's disease. Biology and treatment, MCFarlane RM, MCGrouther DA, Flint MH (eds). 1990, Churchill Livingstone, Edinburgh pp. 31 47.
33. Betz P, Nerlich A, Wilske J, Tubel J, Wiest I, Penning R, Eisenmenger W. Time-dependent peri-cellular expression of collagen type IV, laminin, and heparan sulfate proteoglycan in myofibroblasts. Int J Legal Med. 1992 105 : 169 72.
34. Berndt A, Kosmehl H, Katenkamp D, Tauchmann V. Appearance of the myofibroblastic phenotype in Dupuytren's disease is associated with a fibronectin, laminin, collagen type IV and tenascin extracellular matrix. Pathobiology. 1994 62 : 55 8.
35. Kosmehl H, Berndt A, Katenkamp D, Mandel U, Bohle R, Gabler U, Celeda D. Differential expression of fibronectin splice variants, oncofetal glycosylated fibronectin and laminin isoforms in nodular palmar fibromatosis. Pathol Res Pract. 1995 191 : 1105 13.
36. Blyweert W, Van der Aa F, Ost D, Stagnaro M, De Ridder D. Interstitial cells of the bladder: the missing link Br J Obstet Gynaecol. 2004 111 : 57 60.
37. Kaye GI, Lane N, Pascal RR. Colonic pericryptal fibroblast sheath: replication, migration, and cytodif-ferentiation of a mesenchymal cell system in adult tissue. Gastroenterology. 1968 54 : 852 65.
38. Marsh MN, Trier JS. Morphology and cell proliferation of subepithelial fibroblasts in adult mouse jejunum. Gastroenterology. 1974 67 : 622 35.
39. Valentich JD, Powell DW. Intestinal subepithelial myofibroblasts and mucosal immunophysiology. Curr Opin Gastroenterol. 1994 10 : 645 51.
40. Powell DW, Mifflin RC, Valentich JD, Crowe SE, Saada JI, West AB. Myofibroblasts. I.Paracrine cells important in health and disease. Am J Physiol. 1999 277 : C1 19.
41. Richman PI, Tilly R, Jass JR, Bodmer WF. Colonic pericrypt sheath cells: characterisation of cell type with new monoclonal antibody. J Clin Pathol. 1987 40 : 593 600.
42. Lazard D, Sastre X, Frid MG, Glukhova A, Thiery J-P, Koteliansky VE. Expression of smooth-muscle specific proteins in myoepithelium and stromal myofibroblasts of normal and malignant breast tissue. Proc Natl Acad Sci USA. 1993 90 : 999 1003.
43. Nakayama H, Miyazaki E, Enzan H. Differential expression of high molecular weight caldesmon in colorectal pericryptal fibroblasts and tumour stroma. J Clin Pathol. 1999 52 : 785 6.
44. Balázs M, Egerszegi P, Vadász G, Kovacs A. Correspondence. Histopathology 1989 14 : 434.
45. Rumessen JJ, Mikkelsen HB, Thuneberg L. Ultrastructure of interstitial cells of Cajal associated with deep muscular plexus of human small intestine. Gastroenterology. 1992 102 : 56 68.
46. Rumessen JJ, Peters S, Thuneberg L. Light- and electron microscopical studies of interstitial cells of Cajal and muscle cells at the submucosal border of human colon. Lab Invest. 1993 68 : 481 95.
47. Huizinga JD, Faussone-Pellegrini M-S. About the presence of interstitial cells of Cajal outside the musculature of the gastrointestinal tract. J Cell Mol Med. 2005 9 : 468 73.
48. Min KW, Seo IS. Intestitial [sic] cells of Cajal in the human small intestine: immunochemical and ultra-structural study. Ultrastruct Pathol. 2003 27 : 67 78.
49. Drake MJ, Hedlund P, Andersson KE, Brading AF, Hussain I, Fowler C, Landon DN. Morphology, phenotype and ultrastructure of fibroblastic cells from normal and neuropathic human detrusor: absence of myofibroblast characteristics. J Urol. 2003 169 : 1573 6.
50. + fibrocytes, α -smooth muscle antigen-positive myofibroblasts, and CD117 expression in the stroma of invasive squamous cell carcinomas of the oral cavity, pharynx, and larynx. Virchows Arch. 2004 444 : 231 4.
51. Kuroda N, Shimasaki N, Miyazaki E, Hamauzu T, Toi M, Hiroi M, Shuin T, Enzan H. The distribution of myofibroblasts and C34-positive stromal cells in normal renal pelvis and ureter and their cancers. Histol Histopathol. 2006 21 : 1303 7.
52. Guber S, Rudolph R. The myofibroblast. Surgery Gynecol Obstet. 1978 146 : 641 9.
53. Martin M, Pujuguet P, Martin F. Role of stromal myofibroblasts infiltrating colon cancer in tumor invasion. Path Res Pract. 1996 192 : 712 7.
54. Mentzel T, Dry S, Katenkamp D, Fletcher CDM. Low-grade myofibroblastic sarcoma. Analysis of 18 cases in the spectrum of myofibroblastic tumors. Am J Surg Pathol. 1998 : 22 : 1228 38.
55. De Wewer O, Mareel M. Role of tissue stroma in cancer cell invasion. J Pathol. 2003 200 : 429 47.
56. Direkze NC, Hodivala-Dilke K, Jeffery R, Hunt T, Poulsom R, Oukrif D, Alison MR, Wright NA. Bone marrow contribution to tumour-associated myofibroblasts and fibroblasts. Cancer Res. 2004 64 : 8492 5.
57. Sappino AP, Schürch W, Gabbiani G. Biology of disease. Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phe-notypic modulations. Lab Invest. 1990 63 : 144 61.
58. O'Shea JD. An ultrastructural study of smooth-muscle-like cells in the theca externa of ovarian follicles in the rat. Anat Rec. 1970 167 : 127 40.
59. Bressler RS. Myoid cells in the capsule of the adrenal gland and in monolayers derived from cultured adrenal capsules. Anat Rec. 1973 177 : 525 32.
60. Aumüller G. Smooth muscle in the male genital tract. Chapter 9: Ultrastructure of smooth muscle, PM Motta (ed Kluwer Academic Publishers, Boston, 1990.
61. Hinz B, Mastrangelo D, Iselin CE, Chaponnier C, Gabbiani G. Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol. 2001 159 : 1009 20.
62. Wang J, Lukse E, Seth A, McCulloch CAG. Use of conditionally immortalized mouse cardiac fibroblasts to examine the effect of mechanical stretch on α-smooth muscle actin. Tissue & Cell. 2001 33 : 86 96.
63. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nature Rev Mol Cell Biol. 2002 3 : 349 63.
64. Ng CP, Hinz B, Swartz MA. Interstitial fluid flow induces myofibroblast differentiation and collagen alignment in vitro. J Cell Sci. 2005 118 : 4731 9.
65. Hinz B. Masters and servants of the force: the role of matrix adhesions in myofibroblast force perception and transmission. Eur J Cell Biol. 2006 85 : 175 81.
66. Beertsen W. Migration of fibroblasts in the periodontal ligament of the mouse incisor as revealed by autoradiography. Arch Oral Biol. 1975 20 : 659 66.
67. Garant PR. Collagen resorption by fibroblasts. J Periodont. 1976 47 : 380 90.
68. Holstein AF, Maekawa M, Nagano T, Davidoff MS. Myofibroblasts in the lamina propria of human seminiferous tubules are dynamic structures of heterogeneous phenotype. Arch Histol Cytol. 1996 59 : 109 25.
69. Komuro T. Re-evalution of fibroblasts and fibroblast-like cells. Anat Embryol. 1990 182 : 103 12.
70. Olumi AE, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR. Carcinoma-associated fibrob-lasts direct tumor progression of initiated human pro-static epithelium. Cancer Res. 1999 59 : 5002 11.
71. Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL. TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science. 2004 303 : 848 51.
72. Desmoulière A, Guyot C, Gabbiani G. The stroma reaction myofibroblast: a key player in the control of tumor cell behaviour. Int J Dev Biol. 2004 48 : 509 17.
73. Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol. 2004 15 : 1 12.
74. Micke P, Ostman A. Tumor-stroma interactions: Cancer-associated fibroblasts as novel targets in anti-cancer therapy? Lung Cancer. 2004 45 : S163 75.
75. Livant DL. Targeting invasion induction as a therapeutic strategy for the treatment of cancer. Curr Cancer Drug Targets. 2005 5 : 489 503.
76. Vittal R, Horowitz JC, Moore BB, Zhang H, Martinez FJ, Toews GB, Standiford TJ, Thannickal VJ. Modulation in prosurvival signaling in fibroblasts by a protein kinase inhibitor protects against fibrotic tissue injury. Am J Pathol. 2005 166 : 367 75.
77. Chaudhary NI, Roth GJ, Hilberg F, Müller-Quernheim J, Prasse A, Zissel G, Schnapp A, Park JE. Inhibition of PDGF, VEGF and FGF-signalling attenuates fibrosis. Eur Respir J. 2007 29 : 976 85.
78. Narine K, De Wewer O, Cathenis K, Mareel M, Van Belleghem Y, Van Nooten G. Transforming growth factor-beta-induced transition of fibroblasts: a model for myofibroblast procurement in tissue valve engineering. J Heart Valve Dis. 2004 13 : 281 9.
79. 1 during differentiation of cardiac fibroblasts to myofibroblasts. Hypertension. 2002 39 : 258 63.
80. Hinz B, Dugina V, Ballestrem C, Wehrle-Haller B, Chaponnier C. α -smooth muscle actin is crucial for focal adhesion maturation in myofibroblasts. Mol Biol Cell. 2003 14 : 2508 19.
81. Hinz B, Gabbiani G. Mechanisms of force generation and transmission by myofibroblasts. Curr Opin Biotechnol. 2003 14 : 538 46.
82. Guarino M, Rubino B, Ballabio G. The role of epithelial-mesenchymal transition in cancer pathology. Pathology. 2007 39 : 305 18.
83. Dingemans KP, Zeeman-Boeschoten IM, Keep RF, Das PK. Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype. Int J Cancer. 1993 54 : 1010 6.
84. Surowiak P, Murawa D, Materna V, Maciejczyk A, Pudelko M, Ciesla S, Breborowicz J, Murawa P, Zabel M, Dietel M, Lage H. Occurence of stromal myofibroblasts in the invasive ductal breast cancer tissue is an unfavourable prognostic factor. Anticancer Res. 2007 27 : 2917 24.
85. Kellermann MG, Sobral LM, da Silva SD, Zecchin KG, Graner E, Lopes MA, Nishimoto I, Kowalski LP, Coletta RD. Myofibroblasts in the stroma of oral squamous cell carcinoma are associated with poor prognosis. Histopathology. 2007 51 : 849 53.
86. Steiner MS, Barrack ER. Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. Mol Endocrinol. 1992 6 : 15 25.
87. Arteaga CL, Hurd SD, Winnier AR, Johnson MD, Fendly BM, Forbes JT. Anti-transforming growth factor (TGF)-β antibodies inhibit breast cancer cell tumorigenicity and increase mouse spleen natural killer activity. J Clin Invest. 1993 92 : 2569 76.
88. Xu X, Wang Y, Chen Z, Sternlicht MD, Hidalgo M, Steffensen B. Matrix metalloproteinase-2 contributes to cancer cell migration on collagen. Cancer Res. 2005 65 : 130 6.
89. Stamenkovic I. Extracellular matrix remodeling: the role of matrix metalloproteinases. J Pathol. 2003 200 : 4458 64.
90. Hildebrand R, Gandhari M, Stroebel P, Marx A, Allgayer H, Arens N. The urokinase-system - role of cell proliferation and apoptosis. Histol Histopathol. 2008 23 : 227 36.
91. Yamada KM, Aota S, Akiyama SK, LaFlamme SE. Mechanisms of fibronectin and integrin function during cell adhesion and migration. Cold Spring Harbor Symposia on Quantitative Biology. 1992 62 : 203 12.
92. Inoue T, Nabeshima K, Shimao Y, Meng JY, Koono M. Regulation of fibronectin expression and splicing in migrating epithelial cells: migrating MDCK cells produce a lesser amount of, but more active, fibronectin. Biochem Biophys Res Comm. 2001 280 : 1262 8.
93. Kilian O, Dahse R, Alt V, Zardi L, Rosenhahn J, Exner U, Battmann A, Schnettler R, Kosmehl H. Expression of EDA+ and EDB+ fibronectin splice variants in bone. Bone. 2004 35 : 1334 45.
94. Kohn EC, Travers LA, Kassis J, Broome U, Klominek J. Malignant effusions are sources of fibronectin and other promigratory and proinvasive components. Diagn Cytopathol. 2005 33 : 300 8.
95. Mhawech P, Dulguerov P, Assaly M, Ares C, Allal AS. EB-D [sic] fibronectin expression in squamous cell carcinoma of the head and neck. Oral Oncol. 2005 41 : 82 8.
96. Saito S, Yamaji N, Yasunaga K, Saito T, Matsumoto S, Katoh M, Kobayashi S, Masuho Y. The fibronectin extra domain A activates matrix metalloproteinase gene expression by an interleukin-1-dependent mechanism. J Biol Chem. 1999 274 : 30756 63.
97. Rønnov-Jessen L, Petersen OW, Koteliansky VE, Bissell MJ. The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. J Clin Invest. 1995 95 : 859 73.
98. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest. 2002 110 : 341 50.
99. Yen T-H, Wright NA. The gastrointestinal tract stem cell niche. Stem Cell Rev. 2006 2 : 203 12.
100. Abe R, Donnelly SC, Peng T, Bucala R, Metz CN. Peripheral blood fibrocytes: differentiation pathway and migration to wound sites. J Immunol. 2001 166 : 7556 62.
101. Yamaguchi Y, Kubo T, Murakami T, Takahashi M, Hakamata Y, Kobayashi E, Yoshida S, Hosokawa K, Yoshikawa K, Itami S. Bone marrow cells differentiate into wound myofibroblasts and accelerate the healing of wounds with exposed bones when combined with an occlusive dressing. Br J Dermatol. 2005 152 : 616 22.
102. Kisseleva T, Uchinami H, Feirt N, Quintana-Bustamente O, Segovia JC, Schwabe RF, Brenner DA. Bone marrow-derived fibrocytes participate in patho-genesis of liver fibrosis. J Hepatol. 2006 45 : 429 38.
103. Möllmann H, Nef HM, Kostin S, von Kalle C, Pilz I, Weber M, Schaper J, Hamm CW, Elsässer A. Bone marrow-derived cells contribute to infarct remodel-ling. Cardiovasc Res. 2006 71 : 661 71.
104. Ishii G, Sangai T, Oda T, Aoyagi Y, Hasebe T, Kanomata N, Endoh H, Okumura C, Okuhara Y, Magae J, Emura M, Ochiya T, Ochiai A. Bone-marrow-derived myofibroblasts contribute to the cancer-induced stromal reaction. Biochem Biophys Res Commun. 2003 309 : 232 40.
105. Gupta PB, Proia D, Cingoz O, Weremowicz J, Naber SP, Weinberg RA, Kuperwasser C. Systemic stromal effects of estrogen promote the growth of estrogen receptor-negative cancers. Cancer Res. 2007 67 : 2062 71.
106. Quan TE, Cowper SE, Bucala R. The role of circulating fibrocytes in fibrosis. Curr Rheumatol Rep. 2006 8 : 145 50.
107. Xu Q, Zhang Z, Davison F, Hu Y. Circulating progenitor cells regenerate endothelium of vein graft atherosclerosis, which is diminished in ApoE-deficient mice. Circ Res. 2003 93 : e76-86.
108. Bentzon JF, Sondergaard CS, Kassem M, Falk E. Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipopro-tein E knockout mice. Circulation. 2007 116 : 2053 61.
109. Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest. 2003 112 : 1776 84.
110. Birchmeier C, Birchmeier W, Brand-Saberi B. Epithelial-mesenchymal transitions in cancer progression. Acta Anat. 1996 156 : 217 26.
111. Ru Y, Eyden BP, Curry A, McWilliam LJ, Coyne JD. Actin filaments in human renal tubulo-interstitial fibrosis: significance for the concept of epithelial-myofibroblast transformation. J submicrosc Cytol Pathol. 2003 35 : 221 33.
112. Willis BC, du Bois RM, Borok Z. Epithelial origin of myofibroblasts during fibrosis in the lung. Proc Am Thorac Soc. 2006 3 : 377 82.
113. Ng Y-Y, Huang T-P, Yang W-C, Chen Z-P, Yang A-H, Mu W, Nikolic-Paterson DJ, Atkins RC, Lan HY. Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats. Kidney Int. 1998 54 : 864 76.
114. Ina K, Kitamura H, Tatsukawa S, Takayama T, Fujikura Y, Shimada T. Transformation of interstitial fibroblasts and tubulointerstitial fibrosis in diabetic nephropathy. Med Electron Microsc. 2002 35 : 87 95.
115. Cheng S, Lovett DH. Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. Am J Pathol. 2003 162 : 1937 49.
116. Zhang C, Meng X, Zhu Z, Liu J, Deng A. Connective tissue growth factor regulates the key events in tubular epithelial to myofibroblast transition in vitro. Cell Biol Int. 2004 28 : 863 73.
117. Forino M, Torregrossa R, Ceol M, Murer L, Vella MD, Prete DD, D'Angelo A, Anglani F. TGFbeta1 induces epithelial-mesenchymal transition, but not myofibroblastic transdifferentiation of human kidney tubular epithelial cells in primary culture. Int J Exp Pathol. 2006 87 : 197 208.