TY - JOUR
T1 - Mitogenic signals for platelet-derived growth factor isoforms in liver fat-storing cells
AU - Pinzani, M.
AU - Knauss, T. C.
AU - Pierce, G. F.
AU - Hsieh, P.
AU - Kenney, W.
AU - Dubyak, G. R.
AU - Abboud, H. E.
PY - 1991
Y1 - 1991
N2 - Platelet-derived growth factor (PDGF), a key mitogen for liver fat-storing cells (FSC), is a dimeric molecule that occurs as homodimers or heterodimers of related polypeptide chains (PDGF-BB, -AB, and -AA). In chronic inflammation of the liver lobule, any of the three dimeric forms of PDGF derived from multiple sources could potentially interact with FSC. We explored the effects of the three different PDGF isoforms on DNA synthesis and early signal transduction pathways potentially related to PDGF mitogenicity in rat liver FSC. PDGF-BB homodimer and -AB heterodimer induced a marked increase in DNA synthesis, whereas the effect of PDGF-AA homodimer was considerably lower. Moreover, the mitogenicity of each isoform proportionally correlated with their effects on phosphoinositide turnover and intracellular Ca2+. Both the PDGF-BB and -AB dimers likely interact with the PDGF-β-receptor, although PDGF-AB requires at least one α-receptor. The low responsiveness to PDGF-AA could not be accounted for by downregulation of the PDGF-α-receptor because FSC expressed very low levels of PDGF-A- and B-chain mRNAs and did not secrete detectable amounts of PDGF activity in the conditioned media. In addition, preincubation of FSC with suramin, a potent inhibitor of PDGF binding to its receptor, failed to increase PDGF-AA-induced DNA synthesis. These results are consistent with a predominant expression of PDGF-β-receptor in liver FSC, that is linked to phospholipase C activation.
AB - Platelet-derived growth factor (PDGF), a key mitogen for liver fat-storing cells (FSC), is a dimeric molecule that occurs as homodimers or heterodimers of related polypeptide chains (PDGF-BB, -AB, and -AA). In chronic inflammation of the liver lobule, any of the three dimeric forms of PDGF derived from multiple sources could potentially interact with FSC. We explored the effects of the three different PDGF isoforms on DNA synthesis and early signal transduction pathways potentially related to PDGF mitogenicity in rat liver FSC. PDGF-BB homodimer and -AB heterodimer induced a marked increase in DNA synthesis, whereas the effect of PDGF-AA homodimer was considerably lower. Moreover, the mitogenicity of each isoform proportionally correlated with their effects on phosphoinositide turnover and intracellular Ca2+. Both the PDGF-BB and -AB dimers likely interact with the PDGF-β-receptor, although PDGF-AB requires at least one α-receptor. The low responsiveness to PDGF-AA could not be accounted for by downregulation of the PDGF-α-receptor because FSC expressed very low levels of PDGF-A- and B-chain mRNAs and did not secrete detectable amounts of PDGF activity in the conditioned media. In addition, preincubation of FSC with suramin, a potent inhibitor of PDGF binding to its receptor, failed to increase PDGF-AA-induced DNA synthesis. These results are consistent with a predominant expression of PDGF-β-receptor in liver FSC, that is linked to phospholipase C activation.
KW - Phospholipase C activation
KW - Platelet-derived growth factor-signal transduction
KW - Suramin
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U2 - 10.1152/ajpcell.1991.260.3.c485
DO - 10.1152/ajpcell.1991.260.3.c485
M3 - Article
C2 - 2003575
AN - SCOPUS:0025825254
VL - 260
SP - C485-C491
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6143
IS - 3 29-3
ER -