title: The anti-fibrotic effect of bone morphogenic protein-7(BMP-7) on liver fibrosis.
abstract: Background/Aims : Transforming growth factor-β1 (TGF-β1) 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-β1 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-β1 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-β1 overexpression and the inhibition of TGF-β1 triggered intracellular signalling in hepatic cells.
authors.affiliation: Division of Gastroenterology, East Hospital of Tongji University School of Medicine, Shanghai 200120, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhong
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wang
authors.forename: Shenglan
authors.initials: S
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Hengjun
authors.initials: H
authors.lastname: Gao
authors.forename: Changqing
authors.initials: C
authors.lastname: Yang
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000008:administration & dosage*; D044967:Serum / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine / Q000097:blood; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D055419:Bone Morphogenetic Protein 7; D024042:Collagen Type I; D024061:Collagen Type III; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1
keywords: bone morphogenic protein-7; epithelial-to-mesenchymal transition; extracellular matrix.; hepatic stellate cell; hepatocytes; liver fibrosis; transforming growth factor beta 1