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学科主题: 临床医学
题名:
The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+stem cells
作者: Zhao, Bing1; Qi, Zhen1; Li, Yehua1; Wang, Chongkai2; Fu, Wei2; Chen, Ye-Guang1
刊名: NATURE COMMUNICATIONS
发表日期: 2015-05-01
DOI: 10.1038/ncomms8166
卷: 6
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: DEXTRAN SULFATE SODIUM ; EMBRYONIC STEM-CELLS ; IN-VITRO ; INTESTINAL INFLAMMATION ; ULCERATIVE-COLITIS ; SELF-RENEWAL ; INHIBITOR ; MICE ; CANCER ; COLON
英文摘要:

Lgr5+ stem cells are crucial to gut epithelium homeostasis, and therapies targeting these cells hold promise for treatment of gastrointestinal diseases. Here we report that the non-muscle-myosin-II (NMII) heavy chain Myh9 accumulates at epithelial injury sites in mice distal colon treated with dextran sulphate sodium (DSS). Gut-epithelium-specific Myh9 monoallelic deletion alleviates DSS-induced colonic crypt damage and acute colitis. Consistently, the NMII inhibitor blebbistatin can improve the survival of Lgr5+ stem cells and the growth of Lgr5 organoids. Mechanistically, inhibition of NMII by blebbistatin or Myh9 monoallelic deletion activates Akt through Rac1 and PAK1, which is essential for the survival and pluripotency of Lgr5+ cells. These results establish a critical role of the Myh9-Rac1-PAK1-Akt pathway in the maintenance of Lgr5+ stem cells. As blebbistatin can mitigate DSS-induced colitis and preserve Lgr5+ colonic stem cells in vivo, our findings provide a potential therapeutic intervention of gastrointestinal epithelium injury and degenerative diseases.

语种: 英语
所属项目编号: 2011CBA01104 ; 31330049 ; 31221064
项目资助者: 973 Program ; National Natural Science Foundation of China ; Amgen China ; China Postdoctoral Science Foundation
WOS记录号: WOS:000355534400003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/59957
Appears in Collections:北京大学第三临床医学院_普通外科_期刊论文

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作者单位: 1.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China
2.Peking Univ, Hosp 3, Dept Gen Surg, Beijing 100191, Peoples R China

Recommended Citation:
Zhao, Bing,Qi, Zhen,Li, Yehua,et al. The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+stem cells[J]. NATURE COMMUNICATIONS,2015,6.
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