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核受体在炎症性肠病发病机制和治疗中的作用。

Nuclear Receptors in the Pathogenesis and Management of Inflammatory Bowel Disease.

机构信息

Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

出版信息

Mediators Inflamm. 2019 Jan 21;2019:2624941. doi: 10.1155/2019/2624941. eCollection 2019.

Abstract

Nuclear receptors (NRs) are ligand-dependent transcription factors that regulate the transcription of target genes. Previous epidemiological and genetic studies have documented the association of NRs with the risk of inflammatory bowel disease (IBD). Although the mechanisms of action of NRs in IBD have not been fully established, accumulating evidence has demonstrated that NRs play complicated roles in regulating intestinal immunity, mucosal barriers, and intestinal flora. As one of the first-line medications for the treatment of IBD, 5-aminosalicylic acid (5-ASA) activates peroxisome proliferator-activated receptor gamma (PPAR) to attenuate colitis. The protective roles of rifaximin and rifampicin partly depend on promoting pregnane X receptor (PXR) expression. The aims of this review are to discuss the roles of several important NRs, such as PPAR, PXR, vitamin D receptor (VDR), farnesoid X receptor (FXR), and RAR-related orphan receptor gammat (RORt), in the pathogenesis of IBD and management strategies based on targeting these receptors.

摘要

核受体(NRs)是配体依赖性转录因子,可调节靶基因的转录。先前的流行病学和遗传学研究已经证明了 NRs 与炎症性肠病(IBD)风险之间的关联。尽管 NRs 在 IBD 中的作用机制尚未完全确定,但越来越多的证据表明,NRs 在调节肠道免疫、黏膜屏障和肠道菌群方面发挥着复杂的作用。5-氨基水杨酸(5-ASA)作为治疗 IBD 的一线药物之一,通过激活过氧化物酶体增殖物激活受体γ(PPAR)来减轻结肠炎。利福昔明和利福平的保护作用部分依赖于促进孕烷 X 受体(PXR)的表达。本综述旨在讨论几种重要的 NRs(如 PPAR、PXR、维生素 D 受体(VDR)、法尼醇 X 受体(FXR)和 RAR 相关孤儿受体γt(RORγt))在 IBD 发病机制中的作用,以及基于这些受体的治疗策略。

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