Crosstalk between PDGF and IGF-I receptors in rat liver myofibroblasts: implication for liver fibrogenesis

Laboratory Investigation; a Journal of Technical Methods and Pathology
Ruslan NovosyadlyyJens-Gerd Scharf

Abstract

Insulin-like growth factor I (IGF-I) and platelet-derived growth factor (PDGF) have been identified as significant mitogens for liver myofibroblasts (LMFs), one of the cell populations playing a role in liver fibrogenesis. In the present work, we aimed to elucidate a possible interaction between PDGF receptor (PDGFR) and IGF-I receptor (IGF-IR) signaling in LMFs. Among different rat liver cells, PDGFR alpha- and beta-subunits were mainly expressed in hepatic stellate cells and LMFs, and were upregulated during their in vitro cultivation. In LMFs, PDGF-BB (10 ng/ml) stimulated DNA synthesis approximately two-fold and this effect was similar to that of IGF-I. IGF-I and PDGF-BB differentially affected IGF-IR and PDGFR signaling. High concentrations of IGF-I decreased levels of IGF-IR and IRS-1 and inhibited the expression and activation of PDGFRalpha. PDGF-BB prevented IGF-I-induced downregulation of the IGF-IR, but did not affect expression of its cognate receptor subunits. Transphosphorylation of PDGFR and IGF-IR was not observed. PDGF effectively activated terminal MAP kinases, PI3 kinase and Akt kinase, whereas IGF-I demonstrated weaker effects. PLCgamma(1) was phosphorylated only in response to PDGF, but not to IGF-I. In rat ...Continue Reading

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Citations

May 7, 2011·Cell Adhesion & Migration·Pradipta GhoshMarilyn G Farquhar
Mar 8, 2014·Acta Cirúrgica Brasileira·Rosi Aparecida Nunes AcharJosé Lucio Martins Machado
May 9, 2012·Laboratory Investigation; a Journal of Technical Methods and Pathology·Monika KwiecinskiMargarete Odenthal
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Jul 14, 2007·The Journal of Biological Chemistry·Mouad EdderkaouiAnna S Gukovskaya
Oct 11, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Masaki Saito, Wataru Otsu
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Jul 22, 2011·Archives of Oral Biology·Fawad JavedKhalid Al-Hezaimi

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