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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, RESULTS. Meshes: Actins, Adenoviridae, Animals, Bone Morphogenetic Protein 7, Bone Morphogenetic Proteins, Carrier Proteins, Cells, Cultured, Collagen Type I, Gene Expression, Gene Transfer Techniques, Genetic Therapy, Genetic Vectors, Hepatocytes, Humans, Inhibitor of Differentiation Protein 2, Liver Cirrhosis, Male, Mice, Mice, Transgenic, Mitochondrial Proteins, RNA, Messenger, Rats, Rats, Wistar, Signal Transduction, Thioacetamide, Transforming Growth Factor beta.
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Does adenovirus-mediated expression of BMP-7 suppress the development of liver fibrosis in rats? Context: 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 (TGFbeta) plays a pivotal role in extracellular matrix production, but bone morphogenetic protein (BMP)-7, a member of the TGFbeta superfamily, can antagonise the fibrogenic activity of TGFbeta. In this study, we examined whether adenovirus-mediated overexpression of BMP-7 (Ad-BMP-7) antagonised the effect of TGFbeta in vitro and in vivo. 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 TGFbeta, 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.
assistant
These data demonstrate that BMP-7, Smad 1/5/8 and Ids interact to antagonise hepatic fibrogenesis. Final Decision: yes