Platelet-derived growth factor receptor expression in hepatic stellate cells: How too much of a good thing can be bad

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Abstract
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 (CCI4). In contrast, 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 CCI2-treated animals correlated with mRNA increases. In contrast to lipocytes, endothelial cells from normal liver expressed low levels of a- and β-receptor subunit mRNA, which did not increase with injury. Using a P-PDGFR antibody, receptor protein could be identified within fibrotic septa in CCI2-treated animals in regions where cells expressed proliferating cell nuclear antigen (PCNA). In cultured lipocytes activated by growth on uncoated plastic, PPDGFR 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 uiuo and in primary culture. (J. Clin. Invest. 1994; 94:1563-1569.)

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