Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats

@article{citeulike:2184627, abstract = {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-{beta} (TGF{beta}) plays a pivotal role in extracellular matrix production, but bone morphogenetic protein (BMP)-7, a member of the TGF{beta} superfamily, can antagonise the fibrogenic activity of TGF{beta}. Aim: In this study, we examined whether adenovirus-mediated overexpression of BMP-7 (Ad-BMP-7) antagonised the effect of TGF{beta} 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 {alpha}-actin in the presence or absence of TGF{beta}, 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. 10.1136/gut.2006.092460}, author = {Kinoshita, Kohji and Iimuro, Yuji and Otogawa, Kohji and Saika, Shizuya and Inagaki, Yutaka and Nakajima, Yuji and Kawada, Norifumi and Fujimoto, Jiro and Friedman, Scott L. and Ikeda, Kazuo }, citeulike-article-id = {2184627}, doi = {http://dx.doi.org/10.1136/gut.2006.092460}, journal = {Gut}, month = {May}, number = {5}, pages = {706--714}, posted-at = {2008-01-01 08:52:32}, priority = {2}, title = {Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats}, url = {http://dx.doi.org/10.1136/gut.2006.092460}, volume = {56}, year = {2007} }

TY - JOUR ID - citeulike:2184627 L3 - citeulike-article-id:2184627 TI - Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats JF - Gut VL - 56 IS - 5 SP - 706 EP - 714 N2 - 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-{beta} (TGF{beta}) plays a pivotal role in extracellular matrix production, but bone morphogenetic protein (BMP)-7, a member of the TGF{beta} superfamily, can antagonise the fibrogenic activity of TGF{beta}. Aim: In this study, we examined whether adenovirus-mediated overexpression of BMP-7 (Ad-BMP-7) antagonised the effect of TGF{beta} 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 {alpha}-actin in the presence or absence of TGF{beta}, 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. 10.1136/gut.2006.092460 AU - Kinoshita, Kohji AU - Iimuro, Yuji AU - Otogawa, Kohji AU - Saika, Shizuya AU - Inagaki, Yutaka AU - Nakajima, Yuji AU - Kawada, Norifumi AU - Fujimoto, Jiro AU - Friedman, Scott AU - Ikeda, Kazuo PY - 2007/05/01/ UR - http://dx.doi.org/10.1136/gut.2006.092460 ER -