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

Leptin 0301 basic medicine Gene Expression Regulation/drug effects Messenger/metabolism Ligands Cell Proliferation/drug effects Extracellular Signal-Regulated MAP Kinases/metabolism Liver/drug effects Models Receptors Thiazolidinediones/pharmacology Phosphorylation Extracellular Signal-Regulated MAP Kinases Cells, Cultured Platelet-Derived Growth Factor 0303 health sciences Cultured Blotting Phosphorylation/drug effects Cell Differentiation Leptin/pharmacology Liver Actins/metabolism Cell Surface/genetics* Receptors, Leptin Sterol Regulatory Element Binding Protein 1 Western Platelet-Derived Growth Factor/pharmacology Cells Blotting, Western Liver/cytology 610 Receptors, Cell Surface Models, Biological Hypoglycemic Agents/pharmacology 03 medical and health sciences Sterol Regulatory Element Binding Protein 1/genetics Humans Hypoglycemic Agents RNA, Messenger PPAR gamma/agonists Cell Proliferation Liver/metabolism* Biological Actins PPAR gamma Gene Expression Regulation Cell Differentiation/drug effects RNA Messenger/genetics PPAR gamma/metabolism*
DOI: 10.1007/s00418-007-0282-x Publication Date: 2007-03-29T14:26:23Z
ABSTRACT
Leptin is a peptide known to play a profibrogenic role in hepatic stellate cells (HSCs). Peroxisome-proliferator activated receptor (PPAR)-gamma 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-gamma 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-gamma 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-gamma 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.
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