A peroxisome-proliferator activated receptor-gamma ligand could regulate the expression of leptin receptor on human hepatic stellate cells.
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.
Lee
Jung Il
JI
Division of Gastroenterology, Department of Internal Medicine, Center for Advanced Education Inha University College of Medicine by BK-21 project, 7-206, 3rd St., Sinheung-Dong, Jung-Gu, Incheon, 400-711, South Korea.
Paik
Yong-Han
YH
Lee
Kwan Sik
KS
Lee
Jin Woo
JW
Kim
Yong Soo
YS
Jeong
Seok
S
Kwon
Kye Sook
KS
Lee
Dong Haeng
DH
Kim
Hyung Gil
HG
Shin
Yong Woon
YW
Kim
Min Ah
MA
D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008954:Models, Biological; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D054411:Receptors, Leptin; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology
D000199:Actins; D007004:Hypoglycemic Agents; C515448:LEPR protein, human; D020738:Leptin; D008024:Ligands; D047495:PPAR gamma; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D051780:Sterol Regulatory Element Binding Protein 1; D045162:Thiazolidinediones; D048049:Extracellular Signal-Regulated MAP Kinases; C039671:ciglitazone