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学科主题: 基础医学
题名:
Blockade of the Ras-Extracellular Signal-Regulated Kinase 1/2 Pathway Is Involved in Smooth Muscle 22 alpha-Mediated Suppression of Vascular Smooth Muscle Cell Proliferation and Neointima Hyperplasia
作者: Dong, Li-Hua1; Wen, Jin-Kun1; Liu, George5,6; McNutt, Michael A.4; Miao, Sui-Bing1; Gao, Rui1; Zheng, Bin1; Zhang, Hailin2; Han, Mei1
关键词: smooth muscle 22 alpha Ras ; vascular smooth muscle cells ; proliferation ; neointimal hyperplasia
刊名: ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
发表日期: 2010-04-01
DOI: 10.1161/ATVBAHA.109.200501
卷: 30, 期:4, 页:683-691
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Hematology ; Peripheral Vascular Disease
研究领域[WOS]: Hematology ; Cardiovascular System & Cardiology
关键词[WOS]: ACTIN-BINDING ; CAROTID ARTERIES ; RETINOIC ACID ; GENE DELIVERY ; PROTEIN ; DIFFERENTIATION ; EXPRESSION ; INJURY ; ACTIVATION ; CYCLE
英文摘要:

Objective-Vascular smooth muscle cells (VSMCs) can switch between differentiated and dedifferentiated phenotypes, and this phenotype switch is believed to be essential for repair of vascular injury. We studied the inhibitory effect of smooth muscle 22 alpha (SM22 alpha) on VSMC proliferation in vitro and in vivo and explored the potential molecular mechanisms of this effect.

Methods and Results-By using coimmunoprecipitation and glutathione S-transferase pull-down assays, we have shown that SM22 alpha binds to Ras in SM22 alpha-overexpressed VSMCs in the presence or absence of platelet-derived growth factor-BB stimulation. SM22 alpha arrested cell cycle progression through segregation of Ras with Raf-1 and downregulation of the Raf-1-MEK1/2-extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase signaling cascade. The inhibitory effect of SM22 alpha on VSMC proliferation was verified in vivo. The infection of rat carotid arteries with recombinant adenovirus encoding SM22 alpha inhibited neointimal hyperplasia via suppression of the Raf-1-MEK1/2-extracellular signal-regulated kinase 1/2 signaling pathway.

Conclusion-These findings suggest that high expression of SM22 alpha inhibits cell proliferation via reduction of the response to mitogen stimuli in VSMCs and provide a novel mechanism by which VSMCs maintain their contractile phenotype and resist mitogenic stimuli in an SM22 alpha-dependent manner. (Arterioscler Thromb Vasc Biol. 2010; 30: 683-691.)

语种: 英语
所属项目编号: 30770787 ; 30670845 ; C2005000722 ; C2006000814 ; 2008CB517402
项目资助者: National Natural Science Foundation of China ; Hebei Province Natural Science Foundation ; "973" Program of China
WOS记录号: WOS:000275712500010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61361
Appears in Collections:基础医学院_心血管所_期刊论文

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作者单位: 1.Hebei Med Univ, Inst Basic Med, Dept Biochem & Mol Biol, Shijiazhuang 050017, Peoples R China
2.Hebei Med Univ, Inst Basic Med, Dept Pharmacol, Shijiazhuang 050017, Peoples R China
3.Peking Univ, Inst Cardiovasc Sci, Dept Physiol, Beijing 100871, Peoples R China
4.Peking Univ, Sch Basic Med Sci, Dept Pathol, Beijing 100871, Peoples R China
5.Peking Univ, Sch Basic Med Sci, China Adm Educ, Beijing 100871, Peoples R China
6.Peking Univ, Sch Basic Med Sci, Key Lab Cardiovasc Sci, Beijing 100871, Peoples R China

Recommended Citation:
Dong, Li-Hua,Wen, Jin-Kun,Liu, George,et al. Blockade of the Ras-Extracellular Signal-Regulated Kinase 1/2 Pathway Is Involved in Smooth Muscle 22 alpha-Mediated Suppression of Vascular Smooth Muscle Cell Proliferation and Neointima Hyperplasia[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2010,30(4):683-691.
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