Effects Of Bone Morphogenetic Protein-7 And Danshensu On The Inhibition Of Hepatic Fibrosis

Objective: To investigate the anti-hepatic fibrosis mechanisms of bone morphogenetic protein-7 (BMP-7) signaling pathway by exploring the effects of BMP-7 on the signaling of TGFβand the effects of danshensu on the expression of BMP receptor in human hepatic stellate cell LX-2.Method: LX-2 cells were cultured in vitro. Then the LX-2 cells were treated by different concentrations of BMP-7(20-80ng/ml); TGFβ1 (5ng/ml), also TGFβ1 (5ng/ml) with BMP-7(20-80ng/ml) and with danshensu (0.0625-0.25mmol/L) for 48h. The proliferation of LX-2 was measured by Cell counting kit-8(CCK-8). The expressions ofα-smooth muscle actin (α-SMA) and collagenⅠof each group were detected by immunocytochemical assay. RT-PCR was applied to determine the expressions of TGF receptorⅠ,Ⅱ(TβRⅠ,TβRⅡ) ; Smad 3, 7 mRNAs and the expression of BMP receptorⅡ(BMPRⅡ) mRNAs in corresponding groups. Results: The proliferative activity of LX-2 cells in TGFβ1 group showed no significant change comparing to the control group, and BMP-7 inhibited the proliferation of LX-2 cells in a dose-dependent manner. TGFβ1 increased the expressions ofα-SMA and collagenⅠ, while BMP-7 and danshensu antagonized this effect in a dose-dependent manner (P<0.01, P<0.05). BMP-7 showed its impacts of repressing the up-expression of Smad3 (P<0.01) and down-expression of Smad7 (P<0.01) mRNAs induced by TGFβ1 in a dose-dependent manner, but showed no significant impacts on the increasing of TβRⅠand TβRⅡmRNAs induced by TGFβ1 (P>0.05). TGFβ1 decreased the expression of BMPRⅡmRNAs, but danshensu had an opposite impacts.Conclusions: BMP-7 inhibits the proliferation, activation and collagenⅠexpression of HSCs with the possible mechanism of decreasing the Smad3 expression and increasing the Smad7 expression, then depresses the fibrosis promotion effect of TGFβ. Danshensu inhibits the activation and expression of collagenⅠin HSCs by antagonizing the TGFβinducing down regulation of BMPRⅡexpression.