Non-muscle myosin heavy chain 9 maintains intestinal homeostasis by preventing epithelium necroptosis and colitis adenoma formation.
Non-muscle myosin heavy chain 9 maintains intestinal homeostasis by preventing epithelium necroptosis and colitis adenoma formation.
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非肌肉肌球蛋白重链 9 通过防止上皮坏死和结肠炎腺瘤形成来维持肠道稳态
DOI：
10.1016/j.stemcr.2021.03.027
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发表时间：
2021-05-11
影响因子：
5.9
通讯作者：
Chen YG
中科院分区：
文献类型：
--
作者：
Wang S;Li S;Li Y;Jiang Q;Li X;Wang Y;Han JD;Liu Y;Chen YG
非肌肉肌球蛋白IIA在细胞粘附、细胞迁移和组织结构中起重要作用。我们先前表明，非肌肉肌球蛋白II Myh 9重链的低活性有利于LGR 5+肠干细胞的维持。然而，Myh 9在成年小鼠肠上皮中的功能在很大程度上尚不清楚。在这项研究中，我们使用了诱导Villin-creERT 2敲除的方法，删除Myh 9在成年小鼠肠上皮细胞，并观察到纯合删除Myh 9导致结肠炎样的形态学变化，导致高敏感性葡聚糖硫酸钠，并促进结肠炎相关的腺瘤形成在结肠。Myh 9缺失扰乱细胞连接，损害肠腔屏障完整性，促进上皮细胞坏死性凋亡。一致地，这些变化可以通过Ripk 3敲除部分挽救。我们的研究结果表明，Myh 9是维持肠上皮完整性和预防细胞坏死所必需的。Myh 9的纯合缺失导致肠中结肠炎样表型Myh 9缺乏导致Lgr 5+细胞群减少和潘氏细胞脱位Myh 9对于维持肠上皮完整性至关重要Myh 9缺失导致对DSS的高敏感性和结肠炎腺瘤形成Wang et al.报道Myh 9主要通过防止细胞坏死和炎症来维持肠上皮完整性。Myh 9缺陷导致细胞连接破坏和结肠炎样表型以及相关腺瘤的发展。
Non-muscle myosin IIA plays an important role in cell adhesion, cell migration, and tissue architecture. We previously showed that low activity of the heavy chain of non-muscle myosin II Myh9 is beneficial to LGR5+ intestinal stem cell maintenance. However, the function of Myh9 in adult mouse intestinal epithelium is largely unclear. In this study, we used the inducible Villin-creERT2 knockout approach to delete Myh9 in adult mouse intestinal epithelium and observed that homozygous deletion of Myh9 causes colitis-like morphologic changes in intestine, leads to a high sensitivity to dextran sulfate sodium and promotes colitis-related adenoma formation in the colon. Myh9 deletion disturbs cell junctions and impairs intestinal lumen barrier integrity, promoting the necroptosis of epithelial cells. Consistently, these changes can be partially rescued by Ripk3 knockout. Our results indicate that Myh9 is required for the maintenance of intestinal epithelium integrity and the prevention of cell necroptosis. Homozygous deletion of Myh9 causes colitis-like phenotypes in intestine Myh9 deficiency leads to reduced Lgr5+ cell population and Paneth cell dislocation Myh9 is critical for maintenance of intestinal epithelium integrity Myh9 deletion results in high sensitivity to DSS and colitis adenomas formation Wang et al. report that Myh9 is required for maintenance of intestinal epithelial integrity mainly by preventing cell necroptosis and inflammation. Myh9 deficiency leads to cell junction disruption and colitis-like phenotypes and related adenomas development.
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影响因子：
7.2
作者：
Chan FK
通讯作者：
Chan FK
炎症和大肠癌：结肠炎相关的肿瘤。
影响因子：
9
作者：
Grivennikov, Sergei I.
通讯作者：
Grivennikov, Sergei I.
影响因子：
64.8
作者：
Dannappel M;Vlantis K;Kumari S;Polykratis A;Kim C;Wachsmuth L;Eftychi C;Lin J;Corona T;Hermance N;Zelic M;Kirsch P;Basic M;Bleich A;Kelliher M;Pasparakis M
通讯作者：
Pasparakis M
影响因子：
29.7
作者：
Kaser A;Zeissig S;Blumberg RS
通讯作者：
Blumberg RS
影响因子：
4
作者：
Conti, Mary Anne;Adelstein, Robert S.
通讯作者：
Adelstein, Robert S.