Characterization and regulation of insulin-like growth factor binding proteins in human hepatic stellate cells

Journal of Cellular Physiology
A GentiliniS Abboud

Abstract

Cultured hepatic stellate cells (HSCs), the cell type primarily involved in the progression of liver fibrosis, secrete insulin-like growth factor-I (IGF-I) and IGF binding protein (IGFBP) activity. IGF-I exerts a mitogenic effect on HSCs, thus potentially contributing to the fibrogenic process in an autocrine fashion. However, IGF-I action is modulated by the presence of specific IGFBPs that may inhibit and/or enhance its biologic effects. Therefore, we examined IGFBP-1 through IGFBP-6 mRNA and protein expression in HSCs isolated from human liver and activated in culture. Regulation of IGFBPs in response to IGF-I and other polypeptide growth factors involved in the hepatic fibrogenic process was also assessed. RNase protection assays and ligand blot analysis demonstrated that HSCs express IGFBP-2 through IGFBP-6 mRNAs and release detectable levels of IGFBP-2 through IGFBP-5. Because IGF-I, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-beta (TGF-beta) stimulate HSC proliferation and/or matrix production, we tested their effect on IGFBPs released by HSCs. IGF-I induced IGFBP-3 and IGFBP-5 proteins in a time-dependent manner without an increase in the corresponding mRNAs. IGFBP-4 protein levels decrea...Continue Reading

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Citations

Feb 19, 2010·Fibrogenesis & Tissue Repair·Aleksandar SokolovićPiter J Bosma
Oct 12, 2012·PloS One·Marketa JirouskovaRadislav Sedlacek
Mar 11, 2005·American Journal of Veterinary Research·Linda A Dahlgren, Alan J Nixon
Apr 20, 2004·Journal of Cellular Physiology·Ruslan NovosyadlyyJens-Gerd Scharf
May 25, 2004·Laboratory Investigation; a Journal of Technical Methods and Pathology·Bernhard SaileGiuliano Ramadori
Dec 30, 2003·International Journal of Cancer. Journal International Du Cancer·Sjoerd G EliasPaulus A H Van Noord
Apr 30, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hélène Le PabicNathalie Théret
Jan 26, 2006·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Linda A DahlgrenAlan J Nixon
Feb 13, 2002·The American Journal of Pathology·Nicholas A ShackelGeoffrey W McCaughan
Mar 7, 2002·Urology·Thomas R MageeNestor F Gonzalez-Cadavid

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