Inhibitory effects of Arg-Gly-Asp-Ser(RGDS) tetrapeptide on proliferation and collagen synthesis via downregulating focal adhesion kinase in hepatic stellate cell / 解放军医学杂志

ABSTRACT

Objective To investigate the inhibitory effect of Arg-Gly-Asp-Ser (RGDS) on proliferation and collagen synthesis stimulated by fibronectin (FN) and the influence on the expression of focal adhesion kinase of hepatic stellate cell (HSC), in order to provide a theoretical ground for its use in prevention and treatment of hepatic fibrosis in clinic. Methods The adhesion rates were determined by toluidine blue colorimetric assay. The effects of RGDS on the proliferation and collagen synthesis of HSC were assessed by ~3H-TdR and 3H-proline incorporation assays, respectively. The FAK mRNA of HSCs was determined by RT-PCR. Results RGDS was found to inhibit the rates of adhesion, while RGES has no such ability; ②The proliferation and collagen synthesis of HSC were inhibited by RGDS in dose and time-dependent manners; ③The expression of FAK in the (25, 50, 100mg/L) RGDS groups was significantly lower than that in the control group at mRNA level. Conclusions RGDS can inhibit proliferation and collagen synthesis of HSC, and these effects correlate with its anti-adhesion ability. Meanwhile the expression of FAK is also down-regulated significantly. As a signaling molecule, FAK may be involved in the effect of RGDS. This may be one of the underlying mechanisms of anti-fibrosis effect of RGDS.