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法尼酯X受体(FXR)作为肺部疾病的潜在治疗靶点:一篇叙述性综述

Farnesoid X receptor (FXR) as a potential therapeutic target for lung diseases: a narrative review.

作者信息

Cao Yangyang, Xu Yuwen, Zhou Jiaqi, Fu Xiaoyan, Zhang Hongxia, Du Xianhong, Liang Shujuan, Liu Meifang

机构信息

Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, China.

出版信息

J Thorac Dis. 2024 Nov 30;16(11):8026-8038. doi: 10.21037/jtd-24-734. Epub 2024 Nov 29.

Abstract

BACKGROUND AND OBJECTIVE

Farnesoid X receptor (FXR), which is encoded by the gene, is a ligand-activated transcription factor and a member of the nuclear receptor (NR) superfamily. As a receptor for bile acid (BA), FXR has been shown to play a key role in the regulation of BA metabolism, lipid metabolism, and the inflammatory response. This article reviews the roles of FXR in the pathogenesis of various lung diseases, and identifies potential diagnostic indicators or therapeutic targets for these diseases.

METHODS

The PubMed and National Center for Biotechnology Information (NCBI) online databases were searched to retrieve relevant articles published from 2000 to 2024.

KEY CONTENT AND FINDINGS

FXR was originally found to be expressed in BA-targeted organs, such as the liver and intestine. However, recent studies have shown that FXR is also expressed in "non-classical" BA-targeted organs, such as the lung and blood vessels. FXR is not only involved in the pathophysiology of a series of diseases of the gastrointestinal tract and liver, but is also involved in various lung diseases. Recent evidence suggests that FXR participates in the pathogenesis of lung diseases through multiple mechanisms. In addition, FXR may be a potential therapeutic target for some lung diseases. For example, FXR has been reported to promote the occurrence and development of non-small cell lung cancer (NSCLC) by inducing the expression of programmed death ligand 1 (PD-L1) and subsequently suppressing anti-tumor immunity in the tumor microenvironment.

CONCLUSIONS

In this review, we summarized the current knowledge of the roles of FXR in different lung diseases. A better understanding of the roles and mechanisms of FXR in lung diseases will provide new perspectives for the treatment of lung diseases.

摘要

背景与目的

法尼醇X受体(FXR)由该基因编码,是一种配体激活的转录因子,属于核受体(NR)超家族成员。作为胆汁酸(BA)的受体,FXR已被证明在BA代谢、脂质代谢及炎症反应的调节中起关键作用。本文综述了FXR在各种肺部疾病发病机制中的作用,并确定这些疾病潜在的诊断指标或治疗靶点。

方法

检索PubMed和美国国立生物技术信息中心(NCBI)在线数据库,以获取2000年至2024年发表的相关文章。

关键内容与研究结果

FXR最初被发现表达于肝脏和肠道等BA靶向器官。然而,最近的研究表明,FXR也在肺和血管等“非经典”BA靶向器官中表达。FXR不仅参与一系列胃肠道和肝脏疾病的病理生理过程,还参与各种肺部疾病。最近的证据表明,FXR通过多种机制参与肺部疾病的发病机制。此外,FXR可能是某些肺部疾病的潜在治疗靶点。例如,据报道,FXR通过诱导程序性死亡配体1(PD-L1)的表达,进而抑制肿瘤微环境中的抗肿瘤免疫,促进非小细胞肺癌(NSCLC)的发生和发展。

结论

在本综述中,我们总结了目前关于FXR在不同肺部疾病中作用的知识。更好地了解FXR在肺部疾病中的作用和机制将为肺部疾病的治疗提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ef7/11635231/535219bd82ae/jtd-16-11-8026-f1.jpg

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