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Int J Clin Exp Pathol 2013;6(5):897-903

Original Article
Inhibitory effect of bone morphogenetic protein-7 on hepatic fibrosis in rats

Sheng-Lan Wang, Chang-Qing Yang, Xiao-Long Qi, Min Yuan, Yi-Zhong Chang, Li Yang, Heng-Jun Gao

Division of Gastroenterology and Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065,
China. Equal contributors.

Received January 5, 2013; Accepted March 19, 2013; Epub April 15, 2013; Published May 1, 2013

Abstract: Aim: Hepatic cirrhosis is a serious clinical problem caused by the accumulation of extracellular matrix, which can ultimately progress
into hepatic failure. Transforming growth factor-beta1 (TGF-β1) plays a pivotal role in extracellular matrix production. Bone morphogenetic
protein-7 (BMP-7), as a member of the TGF-1 superfamily, has been well proved to be capable of reversing renal fibrosis in mice. In this
study, we aim to investigate the potential effect of BMP-7 on hepatic fibrosis in rats. Methods: Sprague-Dawley rats were randomly divided into
five groups. In the hepatic fibrosis model group (n=8), rats was treated with porcine serum at 0.5ml each time, twice a week. In the negative
control group (n=10), rats were intraperitoneally injected with equal amount and frequency saline. Rats were injected with BMP-7 (100 μg/kg
weight) before porcine serum intraperitoneal injection in the preventive group (n=9). For the early (n=10) and late (n=8) treatment group, rats
were received with BMP-7 (100 μg/kg weight) every other day since the second and fourth week respectively after porcine serum injection. After
eight weeks, the degree of liver fibrosis in rats was evaluated and the expression of TGF-β1 in liver tissues was detected by Western blot and
immunohistochemistry. Results: The grade of hepatic fibrosis was significant attenuated by BMP-7 prevention and treatment compared with
the rats in negative control group (P﹤0.05). In addition, the expression of TGF-β1 greatly decreased in the BMP-7 preventive and treatment
groups detected by both Western blot and immunohistochemistry. Conclusions: BMP-7 can attenuate and even prevent the level of hepatic
fibrosis in rats through inhibiting the expression of TGF-β1 in the liver fibrotic tissues. Therefore, it may be a potential clinical drug for the
prevention and treatment of hepatic fibrosis. (IJCEP1301007).

Keywords: Hepatic fibrosis, bone morphogenetic protein-7, transforming growth factor-beta 1, extracellular matrix, hepatic stellate cell

Address correspondence to: Dr. Chang-Qing Yang, 389 Xin Cun Road, Shanghai 200065, China, Tel: +86-21-6611-1076; Fax: +86-21-6611-
1604; E-mail: cqyang@tongji.edu.cn