The Anti-Fibrotic Effect of Bone Morphogenic Protein-7(BMP-7) on Liver Fibrosis

Background/Aims: Transforming growth factor-beta 1 (TGF-beta 1) plays an important role in the pathogenesis of liver fibrosis and cirrhosis. Recombinant human bone morphogenic protein-7 (rhBMP-7) alleviates renal fibrosis and improves kidney function. However, the beneficial effect of BMP-7 on hepatic fibrosis and cirrhosis remains unknown. The purpose of this study was to investigate the prophylactic and therapeutic effects of rhBMP-7 on liver fibrosis and the underlying mechanisms. Methods: Liver fibrosis in the rat model was induced by peritoneal injection of porcine-serum (0.5ml/kg body weight) twice a week over 8 weeks. The effect of rhBMP-7 on hepatic fibrosis was monitored in rhBMP-7 pre-treated and non-treated rats. Pathologic changes were determined by immunohistolocial staining. TGF-beta 1 expression was investigated by immunohistolocial staining, western blotting, and real-time PCR. Collagen secretion was measured by enzyme-linked immunosorbent assay. Results: Liver fibrosis was significantly reduced by rhBMP-7. The secretion of collagen type-I and -III was decreased by rhBMP-7 in hepatic stellate cells (HSCs) but not in hepatocytes. The anti-fibrotic effect of rhBMP-7 on liver fibrosis was resulted by blocking the nuclear accumulation of Smad2/3 or by inhibiting TGF-beta 1 expression in HSCs or hepatocytes. Conclusions: The anti-fibrogenic mechanism of rhBMP-7 in the rat liver fibrosis was depended on the reduction of TGF-beta 1 overexpression and the inhibition of TGF-beta 1 triggered intracellular signalling in hepatic cells.