Role of platelet-derived growth factor alpha in chronic liver injury (144.4)

Platelet-derived growth factor α (PDGFRα) is a tyrosine kinase receptor that plays a role in liver development and regeneration and is upregulated in livers of patients with primary biliary cirrhosis as well as a majority of hepatocellular carcinomas (HCC). Whether PDGFRα upregulation in these settings plays a compensatory or a pathological role is unknown. This question has led us to investigate the role of PDGFRα in chronic liver injury and hepatic fibrosis - a pathogenic process that is a precursor to the development of cirrhosis and HCC. In this study we show that PDGFRα is upregulated in murine liver following bile duct ligation, a model of cholestatic liver injury. In addition we show that PDGFRα and one of its ligands, PDGF-CC, is localized to hepatocytes as well as bile duct epithelial cells. In vivo blockade of PDGFRα in mice using a previously described monoclonal antibody revealed significant attenuation of hepatocellular injury assessed through liver function analysis of animal serum. In contr...