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学科主题: 临床医学
题名:
Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury
作者: Yang, Li1,2; Besschetnova, Tatiana Y.1,3; Brooks, Craig R.1; Shah, Jagesh V.1,3,4; Bonventre, Joseph V.1,4
刊名: NATURE MEDICINE
发表日期: 2010-05-01
DOI: 10.1038/nm.2144
卷: 16, 期:5, 页:535-U27
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology ; Medicine, Research & Experimental
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology ; Research & Experimental Medicine
关键词[WOS]: TISSUE-GROWTH-FACTOR ; ACUTE-RENAL-FAILURE ; MESENCHYMAL TRANSITION ; DNA-DAMAGE ; HISTONE H3 ; P53 ; DISEASE ; REPAIR ; PHOSPHORYLATION ; PROLIFERATION
英文摘要:

Fibrosis is responsible for chronic progressive kidney failure, which is present in a large number of adults in the developed world. It is increasingly appreciated that acute kidney injury (AKI), resulting in aberrant incomplete repair, is a major contributor to chronic fibrotic kidney disease. The mechanism that triggers the fibrogenic response after injury is not well understood. In ischemic, toxic and obstructive models of AKI, we demonstrate a causal association between epithelial cell cycle G2/M arrest and a fibrotic outcome. G2/M-arrested proximal tubular cells activate c-jun NH(2)-terminal kinase (JNK) signaling, which acts to upregulate profibrotic cytokine production. Treatment with a JNK inhibitor, or bypassing the G2/M arrest by administration of a p53 inhibitor or the removal of the contralateral kidney, rescues fibrosis in the unilateral ischemic injured kidney. Hence, epithelial cell cycle arrest at G2/M and its subsequent downstream signaling are hitherto unrecognized therapeutic targets for the prevention of fibrosis and interruption of the accelerated progression of kidney disease.

语种: 英语
所属项目编号: DK39773 ; DK72381 ; DK074030
项目资助者: US National Institutes of Health (NIH) ; International Society of Nephrology
WOS记录号: WOS:000277394700031
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53418
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: 1.Harvard Univ, Brigham & Womens Hosp, Div Renal, Sch Med,Dept Med, Boston, MA 02115 USA
2.Peking Univ, Hosp 1, Div Renal, Dept Med, Beijing 100871, Peoples R China
3.Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA
4.Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Cambridge, MA USA

Recommended Citation:
Yang, Li,Besschetnova, Tatiana Y.,Brooks, Craig R.,et al. Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury[J]. NATURE MEDICINE,2010,16(5):535-U27.
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