17beta-estradiol inhibits oleic acid-induced rat VSMC proliferation and migration by restoring PGC-1alpha expression.
Estrogen shows a vasoprotective role through inhibiting the proliferation and migration of vascular smooth muscle cells (VSMCs). The mechanism underlying the effect of estrogen, however, is not completely understood. Here, we explored the role of peroxisome proliferator-activated receptor-gamma (PPARgamma) coactivator-1alpha (PGC-1alpha) in estrogen-mediated vasoprotection. Firstly, we showed that oleic acid (OA) decreased PGC-1alpha expression while stimulating VSMC proliferation and migration. In contrast, administration of VSMCs with 17beta-estradiol (E(2), 1 or 10nM) significantly restored OA-decreased PGC-1alpha expression, treatment with 10nM E(2) almost completely abolished OA-induced VSMC proliferation and migration. Secondly, by using PGC-1alpha siRNA, the inhibitory effect of E(2) on VSMC growth is strongly reduced via suppressing PGC-1alpha expression, indicating that E(2) may exert its role through restoring PGC-1alpha. Finally, E(2) (10nM) treatment inhibits OA-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, however, suppression of PGC-1alpha expression abolishes this inhibitory effect of E(2). Our findings demonstrate for the first time that in OA-stimulated rat VSMCs, treatment with E(2) (1 or 10nM) diminishes VSMC proliferation and migration via restoring OA-decreased PGC-1alpha expression. This observation offers a novel molecular basis of the vasoprotective effect of estrogen.
Jiang
Xiaohong
X
Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 # HanKou Road, Nanjing, Jiangsu 210093, People's Republic of China.
Zhang
Yan
Y
Hou
Dongxia
D
Zhu
Lingyun
L
Xu
Wei
W
Ding
Li
L
Qi
Xiaoqiang
X
Sun
Guoxun
G
Liu
Chang
C
Zhang
Junfeng
J
Zen
Ke
K
Xiang
Yang
Y
Zhang
Chen-Yu
CY
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019301:Oleic Acid / Q000494:pharmacology*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004967:Estrogens; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D019301:Oleic Acid; D004958:Estradiol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3