L. Wong et al., INDUCTION OF BETA-PLATELET-DERIVED GROWTH-FACTOR RECEPTOR IN RAT HEPATIC LIPOCYTES DURING CELLULAR ACTIVATION IN-VIVO AND IN CULTURE, The Journal of clinical investigation, 94(4), 1994, pp. 1563-1569
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.