Regulation of vascular smooth muscle cell proliferation by nuclear orphan receptor Nur77.
It has been reported that Nur77 over-expresses in arteriosclerotic lesions and has both pro- and anti-proliferative effects on vascular smooth muscle cells (VSMCs). We investigated the physiological function of Nur77 on proliferation in VSMCs and the effects of atorvastatin on the expression of Nur77. Platelet-derived growth factor (PDGF), a key growth factor mediating VSMC proliferation in atherogenesis and post-angioplasty restenosis, was employed to induce the transcriptional regulation of Nur77 expression in VSMCs and rat carotid artery post-angioplasty restenosis models were used to investigate the effect of atorvastatin on the expression of Nur77 by immunohistochemistry, RT-PCR, and western blot methods. In cell models, we found that PDGF-B induced Nur77 mRNA expression and protein expression through ERK-MAPK-dependent signaling pathways, and atorvastatin attenuated the expression of Nur77 induced by PDGF-B. In the rat model, our data showed Nur77 was up-regulated in neointima, but down-regulated by atorvastatin. Our results indicate that Nur77 promotes VSMC proliferation, and down-regulation of Nur77 by atorvastatin suggests a novel therapy strategy for atherogenesis based on suppression of VSMC proliferation.
Wang
Liyue
L
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No 1277 Jiefang Avenue, Wuhan, 430020 Hubei, China.
Gong
Fan
F
Dong
Xiaoyan
X
Zhou
Wei
W
Zeng
Qiutang
Q
D000818:Animals; D000069059:Atorvastatin; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D006538:Heptanoic Acids; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D010982:Platelet-Derived Growth Factor; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin
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