Leptin induces hypertrophy via p38 mitogen-activated protein kinase in rat vascular smooth muscle cells.
The hypertrophy of vascular smooth muscle cells (VSMCs) is critical in vascular remodeling associated with hypertension, atherosclerosis, and restenosis. Recently, leptin has appeared to play a pivotal role in vascular remodeling. However, the mechanism by which leptin induces hypertrophy in vascular smooth muscle cells is still unknown. We studied the role of leptin as a potential hypertrophic factor in rat VSMCs. In the present study, leptin significantly increased [(3)H]leucine incorporation and the total protein/DNA ratio in VSMCs. The maximal hypertrophic effect was at 100ng/ml of leptin. Leptin induced phosphorylation and activation of p38 mitogen-activated protein (p38 MAP) kinase and of signal transducers and activators of transcription 3 in a concentration- and time-dependent manner. A p38 MAP kinase inhibitor SB203580 significantly inhibited leptin-induced hypertrophy, AG490 (a JAK2 inhibitor) partially inhibited it, and other MAP kinase inhibitors, PD98059 (an ERK inhibitor) and SP600125 (a JNK inhibitor), had no effect. These results indicate that leptin directly stimulates cellular hypertrophy via p38 MAP kinase in rat VSMCs.
Shin
Hye-Jin
HJ
Yonsei Research Institute of Aging Science, Yonsei University, Seoul 120-749, Republic of Korea.
Oh
Jaewon
J
Kang
Seok Min
SM
Lee
Jong Ho
JH
Shin
Min-Jeong
MJ
Hwang
Ki-Chul
KC
Jang
Yangsoo
Y
Chung
Ji Hyung
JH
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006984:Hypertrophy; D020738:Leptin / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000873:Anthracenes; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D020738:Leptin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; C432165:pyrazolanthrone; D004247:DNA; D048051:p38 Mitogen-Activated Protein Kinases; D007930:Leucine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one