INDUCTION OF BETA-PLATELET-DERIVED GROWTH-FACTOR RECEPTOR IN RAT HEPATIC LIPOCYTES DURING CELLULAR ACTIVATION IN-VIVO AND IN CULTURE

A consistent response to liver injury is the activation of resident me senchymal cells known as lipocytes (Ito, fat-storing cells) into a pro liferating cell type. In cultured lipocytes, platelet-derived growth f actor (PDGF) is the most potent proliferative cytokine, but requires t he activation-dependent expression of its receptor protein (Friedman, S. L., and M, J. P. Arthur. 1989. J. Clin. Invest. 84:1780-1785); the role of PDGF receptor (PDGFR) in liver injury is unknown. We have exam ined PDGFR gene expression in freshly isolated lipocytes during liver injury and correlated these findings with a culture model of cellular activation. Whereas lipocytes from normal rats had no detectable trans cript for the beta-PDGFR subunit, this mRNA was induced within 1 h aft er a dose of carbon tetrachloride (CCl4). In contrast, a subunit mRNA was detected in normal cells, but was unchanged after liver injury. Si milar results were observed in lipocytes from bile duct-obstructed rat s, although beta-PDGFR induction was less marked. By immunoblot, induc tion of beta-PDGFR protein in lipocytes isolated from CCl4-treated ani mals correlated with mRNA increases. In contrast to lipocytes, endothe lial cells from normal liver expressed low levels of alpha- and beta-r eceptor subunit mRNA, which did not increase with injury. Using a beta -PDGFR antibody, receptor protein could be identified within fibrotic septa in CCl4-treated animals in regions where cells expressed prolife rating cell nuclear antigen (PCNA). In cultured lipocytes activated by growth on uncoated plastic, beta-PDGPR transcripts appeared within 3 d after plating, which coincided with the onset of cellular proliferat ion. In contrast, quiescent cells in suspension culture had no detecta ble beta-PDGFR mRNA. These results indicate that beta-PDGF receptor in duction by lipocytes is an early event during hepatic injury in vivo a nd in primary culture.