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The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+stem cells
Zhao, Bing1; Qi, Zhen1; Li, Yehua1; Wang, Chongkai2; Fu, Wei2; Chen, Ye-Guang1
刊名NATURE COMMUNICATIONS
2015-05-01
DOI10.1038/ncomms8166
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
WOS记录号WOS:000355534400003
项目编号2011CBA01104 ; 31330049 ; 31221064
资助机构973 Program ; National Natural Science Foundation of China ; Amgen China ; China Postdoctoral Science Foundation
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/400002259/59957
专题北京大学第三临床医学院_普通外科
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
推荐引用方式
GB/T 7714
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.
APA Zhao, Bing,Qi, Zhen,Li, Yehua,Wang, Chongkai,Fu, Wei,&Chen, Ye-Guang.(2015).The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+stem cells.NATURE COMMUNICATIONS,6.
MLA Zhao, Bing,et al."The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+stem cells".NATURE COMMUNICATIONS 6(2015).
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