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IR@PKUHSC  > 北京大学第二临床医学院  > 心血管内科  > 期刊论文
学科主题: 临床医学
题名:
Nuclear Factor kappa B-Mediated Transactivation of Telomerase Prevents Intimal Smooth Muscle Cell From Replicative Senescence During Vascular Repair
作者: 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
发表日期: 2010-12-01
DOI: 10.1161/ATVBAHA.110.213074
卷: 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
所属项目编号: 2004-3469 ; 2007-3337 ; 2005-6333 ; 20080844 ; 2006-037400 ; 201668
项目资助者: Swedish Research Council ; Swedish Research Link ; Swedish Heart-Lung Foundation ; European Unin (Immunath, AtheroRemo)
WOS记录号: WOS:000284309000048
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62292
Appears in Collections:北京大学第二临床医学院_心血管内科_期刊论文

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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

Recommended Citation:
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.
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