Induction of β-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 mesenchymal cells known as lipocytes (Ito, fat-storing cells) into a proliferating cell type. In cultured lipocytes, platelet-derived growth factor (PDGF) is the most potent proliferative cytokine, but requires the 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 examined 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 transcript for the β-PDGFR subunit, this mRNA was induced within 1 h after a dose of carbon tetrachloride (CCl₄). In contrast, α subunit mRNA was detected in normal cells, but was unchanged after liver injury. Similar results were observed in lipocytes from bile duct-obstructed rats, although β-PDGFR induction was less marked. By immunoblot, induction of β-PDGFR protein in lipocytes isolated from CCl₄- treated animals correlated with mRNA increases. In contrast to lipocytes, endothelial cells from normal liver expressed low levels of α- and β- receptor subunit mRNA, which did not increase with injury. Using a β-PDGFR antibody, receptor protein could be identified within fibrotic septa in CCl₄-treated animals in regions where cells expressed proliferating cell nuclear antigen (PCNA). In cultured lipocytes activated by growth on uncoated plastic, β-PDGFR transcripts appeared within 3 d after plating, which coincided with the onset of cellular proliferation. In contrast, quiescent cells in suspension culture had no detectable β-PDGFR mRNA. These results indicate that β-PDGF receptor induction by lipocytes is an early event during hepatic injury in vivo and in primary culture.