Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

E.   M.   Zardi; L.      Navarini; G.      Sambataro; P.      Piccinni; F.   M.   Sambataro; C.      Spina; A.      Dobrina

Abstract

Complex molecular and cellular mechanisms are involved in the pathway of liver fibrosis. Activation and transformation of hepatic stellate cells (HSCs) are considered the two main reasons for the cause and development of liver fibrosis. The peroxisome proliferator-activated receptors (PPARs) belonging to the family of ligand-activated transcription factors play a key role in liver homeostasis, regulating adipogenesis and inhibiting fibrogenesis in HSCs. Normal transcriptional function of PPARs contributes to maintain HSCs in quiescent phase. A reduced expression of PPARs in HSCs greatly induces a progression of liver fibrosis and an increased production of collagen. Here, we discuss role and function of PPARs and we take into consideration molecular factors able to reduce PPARs activity in HSCs. Finally, although further validations are needed, we illustrate novel strategies available from in vitro and animal studies on how some PPARs-agonists have been proved effective as antifibrotic substances in liver disease.

Keywords: Cytokines, genes, HSCs, ligands, liver fibrosis, microcirculation, PPARs, antifbrotic therapy, transcription factors.