Neutralization of Bone Morphogenetic Protein (BMP)–9 in mouse liver reduces CCl–4 mediated fibrogenesis

BMP9, a member of the TGFβ family of cytokines, is mainly expressed in liver. We therefore investigated responses to BMP9 in vitro in hepatic stellate cells (HSC) and hepatocytes (HC) and in vivo. In vascular endothelial cells and most likely in other cell types as well, BMP9 exerts its effects by binding to, and signaling via ALK1.HSC/HC were isolated from mice livers by collagenase digestion and were analyzed during primary culture. Target genes of BMP9 were identified by micro array analyses (Affymetrix). Neutralization of BMP9/ALK1 signaling in vivo was achieved using an adenovirus expressing the extracellul…