ESRRA是肠道稳态的重要调节因子
  • ESRRA(雌激素相关受体α)缺失小鼠对DSS诱导的结肠炎更为敏感,肠道炎症上调;
  • ESRRA缺失小鼠表现出AMPK的磷酸化下调,TFEB水平降低,肠道组织中线粒体缺陷伴随SQSTM1/p62积累;
  • ESRRA缺失小鼠的肠道菌群组成显著改变,比野生型具有更高的微生物多样性,同居或野生小鼠的粪菌移植能缓解ESRRA缺失小鼠的结肠炎严重性;
  • 溃疡性结肠炎患者的肠道粘膜组织中ESRRA表达显著降低,且与疾病的活动性相关联,说明ESRRA在UC中具有临床相关性。
主编推荐语
章台柳
孤儿核受体ESRRA在线粒体生物合成和自噬功能中非常重要,但其在肠道功能中的作用未知。近期发表在Autophagy的文章,发现ESRRA通过激活自噬通量和控制宿主肠道菌群来改善结肠炎症,是肠道内稳态的关键调节因子。
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
图片
Autophagy [IF:13.391]

ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota

ESRRA(雌激素相关受体α)通过肠道菌群激活自噬通量,是肠道稳态的重要调节因子

10.1080/15548627.2020.1847460

2020-11-10, Article

Abstract & Authors:展开

Abstract:收起
The orphan nuclear receptor ESRRA (estrogen related receptor alpha) is critical in mitochondrial biogenesis and macroautophagy/autophagy function; however, the roles of ESRRA in intestinal function remain uncharacterized. Herein we identified that ESRRA acts as a key regulator of intestinal homeostasis by amelioration of colonic inflammation through activation of autophagic flux and control of host gut microbiota. Esrra-deficient mice presented with increased susceptibility to dextran sodium sulfate (DSS)-induced colitis with upregulation of intestinal inflammation. In addition, esrra-null mice had depressed AMP-activated protein kinase phosphorylation (AMPK), lower levels of TFEB (transcription factor EB), and accumulation of SQSTM1/p62 (sequestosome 1) with defective mitochondria in intestinal tissues. Esrra-deficient mice showed distinct gut microbiota composition and significantly higher microbial diversity than wild-type (WT) mice. Cohousing or fecal microbiota transplantation from WT mice to Esrra-deficient mice ameliorated DSS-induced colitis severity. Importantly, patients with ulcerative colitis (UC) had significantly decreased ESRRA expression in intestinal mucosal tissues that correlated with disease activity, suggesting clinical relevance of ESRRA in UC. Taken together, our results show that ESRRA contributes to intestinal homeostasis through autophagy activation and gut microbiota control to protect the host from detrimental inflammation and dysfunctional mitochondria.

First Authors:
Sup Kim,June-Young Lee

Correspondence Authors:
Jin-Woo Bae,Eun-Kyeong Jo

All Authors:
Sup Kim,June-Young Lee,Seul Gi Shin,Jin Kyung Kim,Prashanta Silwal,Young Jae Kim,Na-Ri Shin,Pil Soo Kim,Minho Won,Sang-Hee Lee,Soo Yeon Kim,Miwa Sasai,Masahiro Yamamoto,Jin-Man Kim,Jin-Woo Bae,Eun-Kyeong Jo

评论