Center for Clinical Pharmacology, Washington University in St. Louis and University of Health Sciences & Pharmacy, St. Louis, MO, 63110, USA.
University of Florida Genetics Institute, Gainesville, FL, 32610, USA.
Acta Pharmacol Sin. 2022 May;43(5):1133-1140. doi: 10.1038/s41401-022-00883-w. Epub 2022 Feb 25.
REV-ERBs are atypical nuclear receptors as they function as ligand-regulated transcriptional repressors. The natural ligand for the REV-ERBs (REV-ERBα and REV-ERBβ) is heme, and heme-binding results in recruitment of transcriptional corepressor proteins such as N-CoR that mediates repression of REV-ERB target genes. These two receptors regulate a large range of physiological processes including several important in the pathophysiology of non-alcoholic steatohepatitis (NASH). These include carbohydrate and lipid metabolism as well as inflammatory pathways. A number of synthetic REV-ERB agonists have been developed as chemical tools and they show efficacy in animal models of NASH. Here, we will review the functions of REV-ERB with regard to their relevance to NASH as well as the potential to target REV-ERB for treatment of this disease.
REV-ERBs 是一种非典型的核受体，它们作为配体调节的转录抑制剂发挥作用。REV-ERBs（REV-ERBα 和 REV-ERBβ）的天然配体是血红素，血红素结合导致转录核心抑制蛋白如 N-CoR 的募集，从而介导 REV-ERB 靶基因的抑制。这两种受体调节广泛的生理过程，包括非酒精性脂肪性肝炎（NASH）的病理生理学中的几个重要过程。这些过程包括碳水化合物和脂质代谢以及炎症途径。已经开发了一些合成的 REV-ERB 激动剂作为化学工具，它们在 NASH 的动物模型中显示出疗效。在这里，我们将回顾 REV-ERB 的功能及其与 NASH 的相关性，以及将 REV-ERB 作为治疗这种疾病的靶点的潜力。
