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

• DOI: 10.1007/s00418-007-0282-x
• Publication Date: 2007-03-29T14:26:23Z
• Authors: Jung Il Lee; Yong-Han Paik; Kwan Sik Lee; Jin Woo Lee; Yong Soo Kim; Seok Jeong; Kye Sook Kwon; Dong Haeng Lee; Hyung Gil Kim; Yong Woon Shin; Min Ah Kim
• Keywords: 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*

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.