A peroxisome-proliferator activated receptor-γ ligand could regulate the expression of leptin receptor on human hepatic stellate cells

Abstract

Leptin is a peptide known to play a profibrogenic role in hepatic stellate cells (HSCs). Peroxisome-proliferator activated receptor (PPAR)-γ ligands are suggested to have an anti-fibrogenic effect on HSCs. Since the association of these two factors in HSC activation has not been demonstrated, we hypothesized that PPAR-γ ligands would suppress leptin-induced HSC activation and regulate leptin receptor expression. Immortalized human HSCs were activated by either leptin or platelet-derived growth factor (PDGF) in one group. In another group, ciglitazone, a PPAR-γ ligand, was treated before the leptin or PDGF stimulation. Proliferation of human HSCs was achieved by both PDGF and leptin, and this could be suppressed by ciglitazone. PPAR-γ mRNA expression was diminished in activated HSCs either by PDGF or leptin, and this was reversed by ciglitazone in both cases. Leptin receptor (OB-R) mRNA expression increased in activated HSCs either by PDGF or leptin, and the expression was inhibited by ciglitazone. Another adipogenic transcription factor, sterol regulatory element-binding protein-1c (SREBP-1c) mRNA expression was decreased either by PDGF or leptin. However, this effect was not reversed by ciglitazone pre-treatment. The inhibitory effect of ciglitazone on leptin-induced HSC proliferation was associated with the reversion of extracellular factor-regulated kinases (ERKs) activation. HSCs were OB-R expressing cells, and ciglitazone could regulate the expression of OB-R mRNA.