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Role of platelet‐derived growth factor alpha in chronic liver injury (144.4)
Author(s) -
Kikuchi Alexander,
Monga Satdarshan
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.144.4
Subject(s) - platelet derived growth factor receptor , liver injury , fibrosis , platelet derived growth factor , cirrhosis , medicine , pathology , hepatic stellate cell , cancer research , downregulation and upregulation , bile duct , growth factor , biology , receptor , biochemistry , gene
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 contrast, analysis of in situ hepatic collagen deposition in these animals reveals increased fibrosis in animals treated with PDGFRα inhibitor, suggesting that fibrosis and myofibroblast activation occurs independently of hepatocellular injury in this model. These findings point towards a dichotomous contribution of PDGFRα signaling in cholestatic liver injury with opposing effects in parenchymal and non‐parenchymal cell compartments. Grant Funding Source : T32: HL094295 ANGIOPATHY TRAINING GRANT; R01: DK095498 ROLE OF PDGFRALPHA IN LIVER PATHO‐BIOLOGY