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Role and Regulation of PDGFRα Signaling in Liver Development and Regeneration.
Awuah PK, Nejak-Bowen KN, Monga SP
Division of Experimental Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Platelet derived growth factor receptor alpha (PDGFRα) is a receptor tyrosine kinase with diverse functions in many organs. Others and we have recently reported PDGFRα activation in a significant subset of hepatocellular carcinomas. However its role in normal liver biology remains elusive. In this report, we investigated whether PDGFRα plays any role during liver development and liver regeneration after partial hepatectomy. We identified high PDGFRα expression and activation during the early stage of liver development. Blockade of this receptor led to enhanced cell death and decreased proliferation in embryonic liver cultures. We identified increased PDGFRα signaling at early times after partial hepatectomy. However its loss in hepatocyte-specific PDGFRα conditional knockouts did not alter regeneration kinetics after partial hepatectomy due to increased EGFR and MET expression and activity as a compensatory mechanism. Intriguingly, such compensation was not evident in liver cancer cells but only in normal hepatocytes. Our work further substantiates the role of PDGFRα during normal liver development and regeneration, while substantiating it as a potential therapeutic target in liver cancer.