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JAK-STAT信号通路对肠道通透性的调节:在炎症性肠病中的致病作用及治疗机遇

JAK-STAT Pathway Regulation of Intestinal Permeability: Pathogenic Roles and Therapeutic Opportunities in Inflammatory Bowel Disease.

作者信息

Lei Hillmin, Crawford Meli'sa S, McCole Declan F

机构信息

Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA 92521, USA.

出版信息

Pharmaceuticals (Basel). 2021 Aug 25;14(9):840. doi: 10.3390/ph14090840.

Abstract

The epithelial barrier forms the interface between luminal microbes and the host immune system and is the first site of exposure to many of the environmental factors that trigger disease activity in chronic inflammatory bowel disease (IBD). Disruption of the epithelial barrier, in the form of increased intestinal permeability, is a feature of IBD and other inflammatory diseases, including celiac disease and type 1 diabetes. Variants in genes that regulate or belong to the JAK-STAT signaling pathway are associated with IBD risk. Inhibitors of the JAK-STAT pathway are now effective therapeutic options in IBD. This review will discuss emerging evidence that JAK inhibitors can be used to improve defects in intestinal permeability and how this plays a key role in resolving intestinal inflammation.

摘要

上皮屏障构成了管腔微生物与宿主免疫系统之间的界面,并且是暴露于许多引发慢性炎症性肠病(IBD)疾病活动的环境因素的首个部位。以肠道通透性增加形式出现的上皮屏障破坏是IBD以及其他炎症性疾病(包括乳糜泻和1型糖尿病)的一个特征。调节JAK-STAT信号通路或属于该信号通路的基因中的变异与IBD风险相关。JAK-STAT通路抑制剂现在是IBD有效的治疗选择。本综述将讨论新出现的证据,即JAK抑制剂可用于改善肠道通透性缺陷,以及这在解决肠道炎症中如何发挥关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef49/8466350/a0b056e637a7/pharmaceuticals-14-00840-g001.jpg

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