MicroRNA-21 increases the expression level of occludin through regulating ROCK1 in prevention of intestinal barrier dysfunction
MicroRNA-21 increases the expression level of occludin through regulating ROCK1 in prevention of intestinal barrier dysfunction
复制标题
MicroRNA-21通过调节ROCK1增加occludin表达水平预防肠道屏障功能障碍
DOI：
10.1002/jcb.27742
复制
发表时间：
2019-03-01
影响因子：
4
通讯作者：
Zhou, Xinke
中科院分区：
文献类型：
--
作者：
Liu, Zhihua;Li, Chao;Zhou, Xinke
目的探讨microRNA（miR）-21对紧密连接（TJ）蛋白表达的影响及其对肠屏障的保护作用。方法检测miR-21抑制和过表达的NCM 460细胞株中TJ蛋白和靶基因的表达。为了进一步验证miR-21的作用，建立了mmu-miR-21肠上皮条件性敲除（IKO）小鼠模型。miR-21在急性粪石性肠梗阻患者的临床标本中均有表达。结果Rho相关蛋白激酶1（ROCK 1）为miR-21的靶基因。miR-21表达水平与TJ蛋白水平呈负相关。miR-21 IKO小鼠TJ蛋白和ROCK 1表达明显降低，表现为肠道炎症反应和肠道屏障功能障碍（均P <0. 05）。临床样品的测定结果与NCM 460细胞系和miR-21 IKO小鼠一致。结论MiR-21可能通过靶向ROCK 1促进TJ蛋白的表达，在体内外对肠屏障功能障碍具有保护作用。
Objective The aim of this study is to investigate the role of molecular mechanism of microRNA (miR)-21 on tight junction (TJ)-proteins and its protective effects on the intestinal barrier. Methods TJ proteins and target genes expression were analyzed in miR-21 inhibition and overexpression NCM460 cell lines. To further verify the role of miR-21, the mmu-miR-21 intestinal epithelial conditional knockout (IKO) mice model was established. MiR-21 expression was detected in clinical specimens of acute stercoral obstruction patients. Results Rho-associated protein kinase 1 (ROCK1) were identified as target genes of miR-21. There is a negative correlation between miR-21 expression level and TJ proteins levels. TJ protein and ROCK1 were significantly decreased in miR-21 IKO mice, which presented intestinal inflammation response and intestinal barrier dysfunction (both P < 0.05). Determination of clinical samples showed consistent results with NCM460 cell line and miR-21 IKO mice. Conclusions MiR-21 could be a protective factor of intestinal barrier dysfunction, which promoting the expression of TJ protein by targeting ROCK1 in vivo and in vitro.