上海交大:自噬如何影响结肠炎和肿瘤发生的分子机制
创作:爱的抉择 审核:Lexi 2019年10月28日
  • BRG1是SWI/SNF染色质重塑复合物的ATP酶组分,可维持肠上皮细胞(IECs)的稳态,预防炎症和肿瘤发生;
  • BRG1在IBD患者的IEC中表达下调;
  • IEC特异性缺失BRG1的小鼠患自发结肠炎,BRG1缺失驱动炎症相关CRC发生,过表达BRG1则抑制结肠炎和CRC的发生;
  • BRG1直接调控Atg16l1、Ambra1、Atg7和Wipi2转录,对自噬体生物发生起重要作用,是肠上皮细胞的自噬检查点;
  • BRG1通过调节自噬来控制IECs中的ROS反应,进而维持屏障完整性。
主编推荐语
Lexi
自噬是影响许多炎症性疾病的综合应激反应的核心组成部分,包括炎症性肠病(IBD)和结直肠癌(CRC),其表观遗传调控的分子机理及其在肠炎中的作用未知。来自上海交通大学的高维强和李力团队近日在Nature Communications杂志发表文章,研究了SWI/SNF染色质重塑复合物的ATP酶组分BRG1如何调节自噬依赖的氧化应激,影响结肠炎症和肿瘤发生。结果证明BRG1可能是一种自噬检查点,与结肠炎的发病机制有关,因此BRG1也可能作为疾病干预的潜在治疗靶点。
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BRG1 attenuates colonic inflammation and tumorigenesis through autophagy-dependent oxidative stress sequestration

BRG1通过抑制自噬依赖的氧化应激降低结肠炎症和肿瘤发生

10.1038/s41467-019-12573-z

2019-10-10, Article

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Autophagy is a central component of integrated stress responses that influences many inflammatory diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). While the core machinery is known, the molecular basis of the epigenetic regulation of autophagy and its role in colon inflammation remain largely undefined. Here, we report that BRG1, an ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for the homeostatic maintenance of intestinal epithelial cells (IECs) to prevent the inflammation and tumorigenesis. BRG1 emerges as a key regulator that directly governs the transcription of Atg16l1, Ambra1, Atg7 and Wipi2, which are important for autophagosome biogenesis. Defective autophagy in BRG1-deficient IECs results in excess reactive oxygen species (ROS), which leads to the defects in barrier integrity. Together, our results establish that BRG1 may represent an autophagy checkpoint that is pathogenetically linked to colitis and is therefore likely a potential therapeutic target for disease intervention.

First Authors:
Min Liu,Tongyu Sun

Correspondence Authors:
Li Li,Wei-Qiang Gao

All Authors:
Min Liu,Tongyu Sun,Ni Li,Junjie Peng,Da Fu,Wei Li,Li Li,Wei-Qiang Gao

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