title: Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture.
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 beta-PDGFR subunit, this mRNA was induced within 1 h after a dose of carbon tetrachloride (CCl4). In contrast, alpha 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 beta-PDGFR induction was less marked. By immunoblot, induction of beta-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 alpha- and beta-receptor 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 proliferating cell nuclear antigen (PCNA). In cultured lipocytes activated by growth on uncoated plastic, beta-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 beta-PDGFR mRNA. These results indicate that beta-PDGF receptor induction by lipocytes is an early event during hepatic injury in vivo and in primary culture.
authors.affiliation: University of California, San Francisco Liver Center Laboratory 94110.
authors.forename: L
authors.initials: L
authors.lastname: Wong
authors.forename: G
authors.initials: G
authors.lastname: Yamasaki
authors.forename: R J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: S L
authors.initials: SL
authors.lastname: Friedman
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002478:Cells, Cultured; D003135:Common Bile Duct; D003251:Constriction, Pathologic; D004727:Endothelium / Q000166:cytology; D005355:Fibrosis / Q000139:chemically induced; D005786:Gene Expression Regulation; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D017479:Receptors, Platelet-Derived Growth Factor