PT  - JOURNAL ARTICLE
AU  - Kohji Kinoshita
AU  - Yuji Iimuro
AU  - Kohji Otogawa
AU  - Shizuya Saika
AU  - Yutaka Inagaki
AU  - Yuji Nakajima
AU  - Norifumi Kawada
AU  - Jiro Fujimoto
AU  - Scott L Friedman
AU  - Kazuo Ikeda
TI  - Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats
AID  - 10.1136/gut.2006.092460
DP  - 2007 May 01
TA  - Gut
PG  - 706--714
VI  - 56
IP  - 5
4099  - http://gut.bmj.com/content/56/5/706.short
4100  - http://gut.bmj.com/content/56/5/706.full
SO  - Gut2007 May 01; 56
AB  - Background: Liver cirrhosis, which is caused by the accumulation of extracellular matrix materials, is a serious clinical problem that can progress to hepatic failure. Transforming growth factor-β (TGFβ) plays a pivotal role in extracellular matrix production, but bone morphogenetic protein (BMP)-7, a member of the TGFβ superfamily, can antagonise the fibrogenic activity of TGFβ. Aim: In this study, we examined whether adenovirus-mediated overexpression of BMP-7 (Ad-BMP-7) antagonised the effect of TGFβ in vitro and in vivo. Methods and results: In primary cultured rat stellate cells and the LX-2 human stellate cell line, induction of BMP-7 by Ad-BMP-7 infection decreased the expression of collagen 1A2 mRNA and smooth muscle α-actin in the presence or absence of TGFβ, via Smad 1/5/8 phosphorylation. BMP-7 triggered the mRNA expression of inhibitors of differentiation 2 (Id2) in LX-2. Although endogenous expression of BMP-7 was hardly detectable, Smad1 and Id2 overexpression increased BMP-7 expression in LX-2. A liver fibrosis model was induced by the repetitive intraperitoneal injection of thioacetamide (200 mg/kg body weight) twice per week for up to 7 weeks. In rats administered Ad-BMP-7 via the tail vein, hydroxyproline content and the areas stained by Sirius red dye in the liver were significantly reduced compared to controls. Ad-Id2 also reduced fibrosis. Conclusion: These data demonstrate that BMP-7, Smad 1/5/8 and Ids interact to antagonise hepatic fibrogenesis.