结肠炎
下调和上调
小RNA
体内
激酶
微阵列
微阵列分析技术
体外
癌症研究
化学
Janus激酶2
贾纳斯激酶
炎症性肠病
细胞生物学
生物
基因
基因表达
免疫学
医学
疾病
生物化学
遗传学
病理
作者
Jie Zhao,Ziyang Lin,Pu Ying,Zhibin Zhao,Haojun Yang,Jun Qian,Yu Gong,Yan Zhou,Yi Dai,Yuwen Jiao,Weiming Zhu,Honggang Wang,Liming Tang
出处
期刊:Journal of Crohn's and Colitis
[Oxford University Press]
日期:2022-10-14
卷期号:17 (4): 593-613
被引量:3
标识
DOI:10.1093/ecco-jcc/jjac154
摘要
Abstract Background Numerous studies have explored the association between circular RNAs [circRNAs] and Crohn’s disease [CD]. However, the pathological role, biological functions, and molecular mechanisms of circRNAs in CD have not been fully elucidated. Methods The circRNA microarray analysis was performed to identify deregulated circRNAs in colon tissues. The identified circRNAs were verified through quantitative real-time polymerase chain reaction [qRT-PCR]. In vivo and in vitro functional studies were performed to verify the role of circSMAD4 in CD and investigate the mechanisms involved. Results We found that circSMAD4 was the most significantly upregulated circRNA. The expression level of circSMAD4 was positively correlated with levels of inflammatory factors. Overexpression of circSMAD4 impaired tight junction [TJ] proteins and enhanced apoptosis of epithelial cells. These effects were reversed by treatment with miR-135a-5p mimic. Mechanistic studies showed that circSMAD4 exerts its effects on CD by ‘sponging’ miR-135a-5p to regulate Janus kinase 2 [JAK2]. Si-circSMAD4 delivery through microspheres ameliorated experimental colitis and protected the intestinal barrier function in IL-10 knockout mice. Conclusion This study shows that circSMAD4 regulates the progression of experimental colitis via the miR-135a-5p/JAK2 signalling axis and it may be a potential therapeutic target.
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