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Int J Med Sci 2013; 10(4):441-450. doi:10.7150/ijms.5765 This issue Cite

Research Paper

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

Lan Zhong2, Xiaolin Wang3, Shenglan Wang1, Li Yang1, Hengjun Gao1, Changqing Yang1✉

1. Division of Gastroenterology and Institute of Digestive Disease, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China;
2. Division of Gastroenterology, East Hospital of Tongji University School of Medicine, Shanghai 200120, China;
3. Special Outpatient Clinic, The Affiliated Hospital of Medical College Qingdao University, Qingdao 266003, China.

✉ Corresponding author: Changqing Yang, M.D., Ph.D., E-mail: cqyangedu.cn Tel: +86-21-6611-1076; Fax: +86-21-6611-1604.

Citation:
Zhong L, Wang X, Wang S, Yang L, Gao H, Yang C. The Anti-Fibrotic Effect of Bone Morphogenic Protein-7(BMP-7) on Liver Fibrosis. Int J Med Sci 2013; 10(4):441-450. doi:10.7150/ijms.5765. https://www.medsci.org/v10p0441.htm
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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.

Keywords: liver fibrosis, hepatic stellate cell, hepatocytes, bone morphogenic protein-7, transforming growth factor beta 1, epithelial-to-mesenchymal transition, extracellular matrix.

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APA
Zhong, L., Wang, X., Wang, S., Yang, L., Gao, H., Yang, C. (2013). The Anti-Fibrotic Effect of Bone Morphogenic Protein-7(BMP-7) on Liver Fibrosis. International Journal of Medical Sciences, 10(4), 441-450. https://doi.org/10.7150/ijms.5765.

ACS
Zhong, L.; Wang, X.; Wang, S.; Yang, L.; Gao, H.; Yang, C. The Anti-Fibrotic Effect of Bone Morphogenic Protein-7(BMP-7) on Liver Fibrosis. Int. J. Med. Sci. 2013, 10 (4), 441-450. DOI: 10.7150/ijms.5765.

NLM
Zhong L, Wang X, Wang S, Yang L, Gao H, Yang C. The Anti-Fibrotic Effect of Bone Morphogenic Protein-7(BMP-7) on Liver Fibrosis. Int J Med Sci 2013; 10(4):441-450. doi:10.7150/ijms.5765. https://www.medsci.org/v10p0441.htm

CSE
Zhong L, Wang X, Wang S, Yang L, Gao H, Yang C. 2013. The Anti-Fibrotic Effect of Bone Morphogenic Protein-7(BMP-7) on Liver Fibrosis. Int J Med Sci. 10(4):441-450.

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