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
AUTHORS (11)
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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CITATIONS (12)
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