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Platelet‐derived growth factor receptor expression in hepatic stellate cells: How too much of a good thing can be bad
Author(s) -
Pinzani Massimo
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840220344
Subject(s) - endocrinology , biology , platelet derived growth factor , medicine , platelet derived growth factor receptor , growth factor , hepatic stellate cell , cytokine , receptor , cell culture , immunology , genetics
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 (CCI 4 ). 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 CCI 2 ‐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 CCI 2 ‐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.)