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HDAC3 在炎症中的作用:机制与治疗意义。

The role of HDAC3 in inflammation: mechanisms and therapeutic implications.

机构信息

Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, United States.

出版信息

Front Immunol. 2024 Jul 10;15:1419685. doi: 10.3389/fimmu.2024.1419685. eCollection 2024.

Abstract

Histone deacetylases (HDACs) are critical regulators of inflammatory gene expression, and the efficacy of pan-HDAC inhibitors has been implicated in various disease conditions. However, it remains largely unclear how HDACs precisely regulate inflammation. To this end, evaluating the isoform-specific function of HDACs is critical, and the isoform-specific targeting could also circumvent the off-target effects of pan-HDAC inhibitors. This review provides an overview of the roles of HDAC3, a class I HDAC isoform, in modulating inflammatory responses and discusses the molecular mechanisms by which HDAC3 regulates inflammation associated with brain pathology, arthritis, cardiovascular diseases, lung pathology, allergic conditions, and kidney disorders. The articles also identify knowledge gaps in the field for future studies. Despite some conflicting reports, the selective inhibition of HDAC3 has been demonstrated to play a beneficial role in various inflammatory pathologies. Exploring the potential of HDAC3 inhibition to improve disease prognosis is a promising avenue requiring further investigation.

摘要

组蛋白去乙酰化酶(HDACs)是炎症基因表达的关键调节因子,泛 HDAC 抑制剂的疗效已被涉及到各种疾病状态。然而,HDACs 如何精确地调节炎症仍然很大程度上不清楚。为此,评估 HDAC 的同工型特异性功能至关重要,同工型特异性靶向也可以避免泛 HDAC 抑制剂的脱靶效应。这篇综述概述了 HDAC3(I 类 HDAC 同工型)在调节炎症反应中的作用,并讨论了 HDAC3 调节与脑病理学、关节炎、心血管疾病、肺病、过敏情况和肾脏疾病相关的炎症的分子机制。文章还确定了该领域未来研究的知识空白。尽管有一些相互矛盾的报告,但选择性抑制 HDAC3 已被证明在各种炎症性疾病中具有有益作用。探索抑制 HDAC3 的潜力以改善疾病预后是一个很有前途的研究方向,需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6301/11266039/b5a16f6acdf5/fimmu-15-1419685-g001.jpg

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