Crosstalk between PDGF and IGF-I receptors in rat liver myofibroblasts: implication for liver fibrogenesis
| Autor: | Giuliano Ramadori, Jens-Gerd Scharf, R Pannem, Jozsef Dudas, R. Novosyadlyy |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Liver Cirrhosis
Platelet-derived growth factor Receptor Platelet-Derived Growth Factor alpha medicine.medical_treatment Becaplermin Cell Culture Techniques Receptor IGF Type 1 chemistry.chemical_compound Insulin-like growth factor Phosphatidylinositol 3-Kinases 0302 clinical medicine Receptors Platelet-Derived Growth Factor Insulin-Like Growth Factor I Receptor Cells Cultured Platelet-Derived Growth Factor 0303 health sciences biology Chemistry Gastroenterology Proto-Oncogene Proteins c-sis 3. Good health Crosstalk (biology) Liver 030220 oncology & carcinogenesis Mitogen-Activated Protein Kinases Myofibroblast Platelet-derived growth factor receptor medicine.medical_specialty macromolecular substances Pathology and Forensic Medicine 03 medical and health sciences Internal medicine medicine Animals Rats Wistar Molecular Biology 030304 developmental biology Dose-Response Relationship Drug Cell Biology DNA Receptor Cross-Talk Fibroblasts Phosphoproteins Fibrosis Rats Endocrinology Gene Expression Regulation Rat liver biology.protein Cancer research Insulin Receptor Substrate Proteins sense organs Proto-Oncogene Proteins c-akt |
| Zdroj: | Laboratory investigation; a journal of technical methods and pathology. 86(7) |
| ISSN: | 0023-6837 |
| Popis: | 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 LMFs, blockade of the IGF-IR via inhibition of the IGF-IR kinase completely abrogated IGF- and PDGF-induced mitogenesis and the ability of PDGF to phosphorylate PLCgamma(1). In conclusion, the presented data demonstrate that the PDGFR signaling requires a functional IGF-IR and that PDGF-BB stabilizes the IGF-IR function through preventing the IGF-I-induced downregulation of the IGF-IR. These interactions might be relevant in vivo for the fibroproliferative response during liver injury. |
| Databáze: | OpenAIRE |
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