Silencing ANGPT2 alleviates ulcerative colitis by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-20 eCollection Date: 2024-01-01 DOI:10.1590/1414-431X2024e13379

Xiaojun Wang, Jian Huang, Jia Liu, Yujie Sun, Xinyi Feng, Yansheng Jin, Weigang Zhou

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Abstract

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

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沉默 ANGPT2 可通过 mTOR 信号通路调节自噬介导的 NLRP3 炎性体失活，从而缓解溃疡性结肠炎。

溃疡性结肠炎（UC）是一种以炎症为特征的疑难肠道疾病，其发病机制复杂多样。血管生成素样蛋白 2（ANGPT2）在炎症性疾病中发挥着重要的调节作用。但迄今为止，ANGPT2在UC中的作用尚未见报道。在探究了 UC 患者血清中 ANGPT2 的表达水平后，研究了 ANGPT2 在右旋糖酐硫酸钠（DSS）诱导的 UC 小鼠中的反应机制。抑制 ANGPT2 表达后，UC 小鼠的临床症状和病理变化得到检测。利用免疫组化、免疫荧光和相关试剂盒对 UC 小鼠的结肠浸润、氧化应激和结肠粘膜屏障进行了评估。最后，还采用 Western 印迹法检测了 mTOR 信号通路和 NLRP3 炎症体相关蛋白。沉默ANGPT2能改善DSS诱导的UC小鼠的临床症状和病理变化，减轻结肠炎症浸润和氧化应激，维持结肠粘膜屏障。ANGPT2对UC疾病的调节作用可能是通过调节mTOR信号通路，从而影响自噬介导的NLRP3炎性体失活。沉默ANGPT2可通过mTOR信号通路调节自噬介导的NLRP3炎性体失活，从而缓解UC。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.