Zinc mediated hepatic stellate cell collagen synthesis reduction through TGF-β signaling pathway inhibition

This study is to investigate the effect and underlying mechanism of Zinc (Zn) on hepatic stellate cell collagen synthesis. The proliferation and collagen synthesis ability of LX-2 cells were detected after adding Zn. The collagen synthesis related proteins of MMP-13 and TIMP1 along with TGF-beta signaling pathway related proteins were detected by Western blot. The role of TGF-beta signaling pathway in collagen synthesis inhibition was identified by TGF-beta RI siRNA silencing. Compared with control group, LX-2 cell proliferation ability was significantly inhibited at all Zn concentrations (50 mu M, 100 mu M and 200 mu M). Zn at 50 mu M did not affect the protein content of alpha SMA and type I collagen while 100 mu M and 200 mu M Zn could significantly inhibit aSMA expression. Compared with control group, gene expression and protein content of MMP-13 in 200 mu M Zn group was significantly increased while no difference in gene expression and protein content of TIMP1 was found. TGF-beta RI content in 200 mu M Zn group was significantly decreased and the protein content of TGF-beta RII was not affected. MMP-13 expression was significantly increased after TGF-beta RI siRNA silencing. Further results showed that in LX-2 cells those TGF-beta RI expression was inhibited, LX-2 cell proliferation ability and the expression of synthesis collagen related proteins of aSMA and type I collagen were greatly decreased. Zn could significantly inhibit the expression of aSMA and type I collagen by inhibiting TGF-beta RI expression and promoting MMP-13 expression.