Peroxisome proliferator-activated receptor-γ cross-regulation of signaling events implicated in liver fibrogenesis

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear receptor with transcriptional activity controlling multiple physical and pathological processes. Recently, PPAR gamma has been implicated in the pathogenesis of liver fibrosis. Its depleted expression has strong associations with the activation and transdifferentiation of hepatic stellate cells, the central event in liver fibrogenesis. Studies over the past decade demonstrate that PPAR gamma cross-regulates a number of signaling pathways mediated by growth factors and adipokines, and cellular events including apoptosis and senescence. These signaling and cellular events and their molecular interactions with PPAR-gamma system are profoundly involved in liver fibrogenesis. We critically summarize these mechanistic insights into the PPAR-gamma regulation in liver fibrogenesis based on the updated findings in this area. We conclude with a discussion of the impacts of these discoveries on the interpretation of liver fibrogenesis and their potential therapeutic implications. PPAR gamma activation could be a promising strategy for antifibrotic therapy. (C) 2011 Elsevier Inc. All rights reserved.