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Nuclear Factor kappa B-Mediated Transactivation of Telomerase Prevents Intimal Smooth Muscle Cell From Replicative Senescence During Vascular Repair
Bu, De-xiu1; Johansson, Maria E.1; Ren, Jingyi1,4; Xu, Da-wei2; Johnson, F. Brad3; Edfeldt, Kristina1; Yan, Zhong-qun1
关键词telomerase nuclear factor-kappa B smooth muscle cell intimal hyperplasia gene expression gene therapy genetically altered mice molecular biology vascular biology
刊名ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
2010-12-01
DOI10.1161/ATVBAHA.110.213074
30期:12页:2604-2610
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]REVERSE-TRANSCRIPTASE GENE ; FIBROBLAST-GROWTH-FACTOR ; CATALYTIC SUBUNIT HTERT ; ARTERIAL INJURY ; C-MYC ; ACTIVATION ; PROLIFERATION ; EXPRESSION ; INDUCTION ; PATHWAY
英文摘要

Objective-To gain insights into mechanisms by which intimal hyperplasia interferes with the repair process by investigating expression and function of the catalytic telomerase reverse transcriptase (TERT) subunit after vascular injury.

Methods and Results-Functional telomerase is essential to the replicative longevity of vascular cells. We found that TERT was de novo activated in the intima of injured arteries, involving activation of the nuclear factor kappa B pathway. Stimulation of the isolated intimal smooth muscle cell (SMC) by basic fibroblast growth factor or tumor necrosis factor alpha resulted in increased TERT activity. This depends on the activation of c-Myc signaling because mutation of the E-box in the promoter or overexpression of mitotic arrest deficient 1 (MAD1), a c-Myc competitor, abrogated the transcriptional activity. Inhibition of nuclear factor kappa B in both intimal SMCs and the injured artery attenuated TERT transcriptional activity through reduction of c-Myc expression. Pharmacological blockade of TERT led to SMC senescence. Finally, depletion of telomerase function in mice resulted in severe intimal SMC senescence after vascular injury.

Conclusion-These results support a model in which vascular injury induces de novo expression of TERT in intimal SMCs via activation of nuclear factor kappa B and upregulation of c-Myc. The resumed TERT activity is critical for intimal hyperplasia. (Arterioscler Thromb Vasc Biol. 2010;30:2604-2610.)

语种英语
WOS记录号WOS:000284309000048
项目编号2004-3469 ; 2007-3337 ; 2005-6333 ; 20080844 ; 2006-037400 ; 201668
资助机构Swedish Research Council ; Swedish Research Link ; Swedish Heart-Lung Foundation ; European Unin (Immunath, AtheroRemo)
引用统计
被引频次:12[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62292
专题北京大学第二临床医学院_心血管内科
作者单位1.Karolinska Univ Hosp, Ctr Mol Med, Cardiovasc Res Unit, S-17176 Stockholm, Sweden
2.Karolinska Univ Hosp, Ctr Mol Med, Hematol Res Unit, S-17176 Stockholm, Sweden
3.Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
4.Peking Univ, Hlth Sci Ctr, Peking Univ People Hosp, Dept Cardiol, Beijing, Peoples R China
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GB/T 7714
Bu, De-xiu,Johansson, Maria E.,Ren, Jingyi,et al. Nuclear Factor kappa B-Mediated Transactivation of Telomerase Prevents Intimal Smooth Muscle Cell From Replicative Senescence During Vascular Repair[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2010,30(12):2604-2610.
APA Bu, De-xiu.,Johansson, Maria E..,Ren, Jingyi.,Xu, Da-wei.,Johnson, F. Brad.,...&Yan, Zhong-qun.(2010).Nuclear Factor kappa B-Mediated Transactivation of Telomerase Prevents Intimal Smooth Muscle Cell From Replicative Senescence During Vascular Repair.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,30(12),2604-2610.
MLA Bu, De-xiu,et al."Nuclear Factor kappa B-Mediated Transactivation of Telomerase Prevents Intimal Smooth Muscle Cell From Replicative Senescence During Vascular Repair".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 30.12(2010):2604-2610.
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