Effects of hepatocyte growth factor on the expression of type I collagen and matrix metalloproteinase-1 in normal and scleroderma dermal fibroblasts.
We investigated the direct effect of hepatocyte growth factor (HGF) on the expression of type I collagen in normal and scleroderma dermal fibroblasts, and analyzed the mechanisms underlying the effect in vitro. HGF did not change the protein expression of type I procollagen in the medium of normal human fibroblasts, whereas it reduced the expression in scleroderma fibroblasts. But mRNA levels and the promoter activity of alpha2(I) collagen gene were not significantly affected by HGF in either of the cells. On the other hand, matrix metalloproteinase-1 expression or activity was increased by HGF in both cells, but HGF had stronger effects in scleroderma fibroblasts than normal fibroblasts. Scleroderma fibroblasts overexpressed c-met protein, the receptor for HGF. The overexpression in scleroderma fibroblasts was abolished by the addition of antisense transforming growth factor (TGF)-beta1 oligonucleotide. Our study indicated that HGF may reduce type I collagen accumulation only in scleroderma fibroblasts by enhancing collagenolysis activity, probably because of the overexpression of c-met because of autocrine TGF-beta signaling. Thus, further investigation of the effects of HGF on collagen metabolism may contribute to the treatment of fibrosis in scleroderma.
Jinnin
Masatoshi
M
Department of Dermatology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. JINNINM-DER@h.u-tokyo.ac.jp
Ihn
Hironobu
H
Mimura
Yoshihiro
Y
Asano
Yoshihide
Y
Yamane
Kenichi
K
Tamaki
Kunihiko
K
D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics*; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000503:physiopathology*
D024042:Collagen Type I; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020781:Matrix Metalloproteinase 1