Effects of hepatocyte growth factor on collagen synthesis and matrix metalloproteinase production in keloids

J Korean Med Sci. 2011 Aug;26(8):1081-6. doi: 10.3346/jkms.2011.26.8.1081. Epub 2011 Jul 27.

Abstract

Keloids are pathologic proliferations of the dermal layer of the skin resulting from excessive collagen production and deposition. Hepatocyte growth factor (HGF) increases the expression of matrix metalloproteinase (MMP)-1 and suppresses collagen synthesis to modulate extracellular matrix turnover. To investigate the anti-fibrotic effects of HGF, we examine the mRNA expression of collagen types I and III and matrix metalloproteinase (MMP-1, MMP-3) on human dermal fibroblast (HDF) cell lines and keloid fibroblasts (KFs, n = 5) after adding various amount of HGF protein. We also evaluated the enzymatic activity of MMP-2, MMP-9 by zymograghy. In HDFs treated with TGF-β1 and HGF protein simultaneously, both type I and III collagen mRNA expression significantly decreased (P < 0.05). Expression of MMP-1, MMP-3 mRNA also decreased. However, the mRNA expression of MMP-1, MMP-3 significantly increased in KFs with increasing amount of HGF in dose dependent manner (P < 0.05). The enzymatic activities of MMP-2 increased with increasing HGF protein in a dose-dependent manner. However, the enzymatic activity of MMP-9 did not change. These results suggest that the anti-fibrotic effects of HGF may have therapeutic effects on keloids by reversing pathologic fibrosis.

Keywords: Collagen; Dermal Fibroblast; Hepatocyte Growth Factor; Keloid Fibroblast; Matrix Metalloproteinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Hepatocyte Growth Factor / pharmacology*
  • Humans
  • Keloid / metabolism*
  • Keloid / pathology
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • RNA, Messenger / metabolism
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • Collagen Type I
  • Collagen Type III
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Hepatocyte Growth Factor
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1