Albumin mediates PPAR-gamma or C/EBP-alpha-induced phenotypic changes in pancreatic stellate cells

Abstract

Activation of quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells is a key event of liver fibrosis. and adipogenic transcription factors, PPAR-gamma and C/EBP-alpha, reverse HSC activation. As albumin was reported to maintain the quiescent phenotype of stellate cells, we examined whether it plays a role in PPAR-gamma and C/EBP-alpha-mediated effects. Pancreatic stellate cells (PSCs) were isolated from rat pancreas and used in their culture-activated phenotype. Forced expression of PPAR-gamma or C/EBP-alpha in PSCs increased albumin mRNA and protein levels by >2 5-fold, which is accompanied with increased C/EBP-beta binding to albumin promoter. PPAR-gamma and C/EBP-alpha also induced a phenotypic switch from activated to quiescent cells and. interestingly, suppression of albumin using short-hairpin RNA (shRNA) blocked their effects Therefore. our findings suggest that albumin may be a downstream effector of PPAR-gamma and C/EBP-alpha in PSCs and that it can be an attractive molecular target for anti-fibrotic therapies. (C) 2009 Elsevier Inc All rights reserved.