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-β signaling pathway related proteins were detected by Western blot. The role of TGF-β signaling pathway in collagen synthesis inhibition was identified by TGF-β RI siRNA silencing. Compared with control group, LX-2 cell proliferation ability was significantly inhibited at all Zn concentrations (50 μM, 100 μM and 200 μM). Zn at 50 μM did not affect the protein content of αSMA and type I collagen while 100 μM and 200 μM Zn could significantly inhibit αSMA expression. Compared with control group, gene expression and protein content of MMP-13 in 200 μM Zn group was significantly increased while no difference in gene expression and protein content of TIMP1 was found. TGF-β RI content in 200 μM Zn group was significantly decreased and the protein content of TGF-β RII was not affected. MMP-13 expression was significantly increased after TGF-β RI siRNA silencing. Further results showed that in LX-2 cells those TGF-β RI expression was inhibited, LX-2 cell proliferation ability and the expression of synthesis collagen related proteins of αSMA and type I collagen were greatly decreased. Zn could significantly inhibit the expression of αSMA and type I collagen by inhibiting TGF-β RI expression and promoting MMP-13 expression.