J Korean Med Sci.  2011 Aug;26(8):1081-1086. 10.3346/jkms.2011.26.8.1081.

Effects of Hepatocyte Growth Factor on Collagen Synthesis and Matrix Metalloproteinase Production in Keloids

• Lee WJ
• Park SE
• Rah DK

• KMID: 1777848
• DOI: http://doi.org/10.3346/jkms.2011.26.8.1081

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-beta1 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.

Keyword

Hepatocyte Growth Factor; Keloid Fibroblast; Dermal Fibroblast; Collagen; Matrix Metalloproteinase

MeSH Terms

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

Figure

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  Fig. 1 The effects of HGF protein on type I and III collagen mRNA expression in the human dermal fibroblast cell lines (A, B) and keloid fibroblasts (C). When TGF-β1 (5 ng/mL) was added simultaneously with HGF protein, type I and III collagen mRNA expression significantly decrease in the HDFs (P < 0.05).

• 

  Fig. 2 The effects of HGF protein on MMP-1 and MMP-3 mRNA expression in the human dermal fibroblast cell lines (A, B) and keloid fibroblasts (C). When TGF-β1 (5 ng/mL) was added to the HDFs simultaneously with HGF protein, MMP-1 and MMP-3 mRNA expression decreased. However, in the KFs, MMP-1 and MMP-3 mRNA expression significantly increased with the administration of HGF (P < 0.05).

• 

  Fig. 3 Three days after adding HGF protein, the enzymatic activities of MMP-2 and MMP-9 were examined by zymography. For the HDFs, MMP-2 activity increased after adding HGF protein except 40 ng, and MMP-9 activity did not changed (A). However, after simultaneously adding TGF-β1, MMP-2 and MMP-9 activity were unchanged (B). In the KFs, (C) MMP-2 activity increased with increasing HGF protein in a dose-dependent manner.

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