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早期生长反应因子-1,心血管疾病中的一个动态通道。

Early growth response-1, a dynamic conduit in cardiovascular disease.

作者信息

Khachigian Levon M

机构信息

Vascular Biology and Translational Research, Department of Pathology, Faculty of Medicine and Health, School of Biomedical Sciences, University of New South Wales, Sydney, NSW, Australia.

出版信息

Front Cardiovasc Med. 2024 Nov 15;11:1487668. doi: 10.3389/fcvm.2024.1487668. eCollection 2024.

Abstract

The transcription factor, early growth response-1 (Egr-1) is the product of a prototypic immediate-early gene that plays an integral role in the pathogenesis of multiple cardiovascular diseases. Egr-1 has been linked with atherogenesis, myocardial ischemia-reperfusion injury, cardiac fibrosis and heart failure. Egr-1 expression is triggered by a host of factors including cytokines, hormones, growth factors, hyperglycaemia, biomechanical forces and oxygen deprivation. Egr-1 is a molecular conduit that links changes in the cellular environment with the inducible expression of genes whose products play a causative role in this inflammatory disease. It is rapidly synthesised, undergoes post-translational modification, interacts with a range of cofactors and drives gene expression. Studies in Egr-1 deficient mice, animal models using DNAzymes, RNA interference, oligodeoxynucleotide decoys, antisense oligonucleotides, and new insights provided by technologies such as single cell RNA sequencing, have shaped our understanding of the importance of Egr-1 in the initiation and progression of cardiovascular disease. This article describes Egr-1's role in various cardiovascular settings and discusses potential mechanisms of action. Given the range of conditions linked to Egr-1, this zinc finger protein may serve as a therapeutic target for intervention.

摘要

转录因子早期生长反应因子1(Egr-1)是一个典型的即刻早期基因的产物,在多种心血管疾病的发病机制中发挥着不可或缺的作用。Egr-1与动脉粥样硬化、心肌缺血再灌注损伤、心脏纤维化和心力衰竭有关。Egr-1的表达由多种因素触发,包括细胞因子、激素、生长因子、高血糖、生物力学力和缺氧。Egr-1是一个分子通道,将细胞环境的变化与基因的诱导表达联系起来,这些基因的产物在这种炎症性疾病中起致病作用。它能快速合成,进行翻译后修饰,与一系列辅因子相互作用并驱动基因表达。对Egr-1基因敲除小鼠的研究、使用脱氧核酶、RNA干扰、寡脱氧核苷酸诱饵、反义寡核苷酸的动物模型,以及单细胞RNA测序等技术提供的新见解,塑造了我们对Egr-1在心血管疾病发生和发展中的重要性的理解。本文描述了Egr-1在各种心血管环境中的作用,并讨论了潜在的作用机制。鉴于与Egr-1相关的一系列病症,这种锌指蛋白可能成为干预的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6db9/11605393/78ba08555800/fcvm-11-1487668-g001.jpg

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