Soluble Arg-Gly-Asp peptides reduce collagen accumulation in cultured rat hepatic stellate cells

Hepatic stellate cells play a central role in the pathogenesis of liver fib rosis, both via production of extracellular matrix proteins and through sec retion of matrix metalloproteinases. In this study, effects of soluble cell adhesion peptides on collagen type I accumulation and on expression of mat rix metalloproteinases were analyzed. First, we revealed the expression of alpha(5)-integrin on hepatic stellate cells by immunostaining. Treatment wi th 100 mu g/ml of soluble Arg-Gly-Asp (RGD) peptides was found to reduce ac cumulation of type I collagen without any effects on its transcriptional le vel in rat hepatic stellate cells, whereas a control peptide Gly-Arg-Gly-Gl u-Ser (GRGES) had no such effect. Soluble RGD peptides also increased the s ecretion of collagenase by stellate cells. These data suggested that reduce d accumulation of type I collagen caused by the RGD peptide ligation to int egrins on hepatic stellate cells was partly due to stimulated expression of collagenase by stellate cells.