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可变剪接在血管平滑肌细胞可塑性中的作用不断扩大。

The Expanding Role of Alternative Splicing in Vascular Smooth Muscle Cell Plasticity.

机构信息

Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Camperdown 2050, Australia.

Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia.

出版信息

Int J Mol Sci. 2021 Sep 23;22(19):10213. doi: 10.3390/ijms221910213.

Abstract

Vascular smooth muscle cells (VSMCs) display extraordinary phenotypic plasticity. This allows them to differentiate or dedifferentiate, depending on environmental cues. The ability to 'switch' between a quiescent contractile phenotype to a highly proliferative synthetic state renders VSMCs as primary mediators of vascular repair and remodelling. When their plasticity is pathological, it can lead to cardiovascular diseases such as atherosclerosis and restenosis. Coinciding with significant technological and conceptual innovations in RNA biology, there has been a growing focus on the role of alternative splicing in VSMC gene expression regulation. Herein, we review how alternative splicing and its regulatory factors are involved in generating protein diversity and altering gene expression levels in VSMC plasticity. Moreover, we explore how recent advancements in the development of splicing-modulating therapies may be applied to VSMC-related pathologies.

摘要

血管平滑肌细胞 (VSMCs) 表现出非凡的表型可塑性。这使它们能够根据环境线索进行分化或去分化。VSMCs 能够在静止的收缩表型和高度增殖的合成状态之间“切换”,这使它们成为血管修复和重塑的主要介质。当它们的可塑性出现病理性改变时,可能会导致心血管疾病,如动脉粥样硬化和再狭窄。随着 RNA 生物学在技术和概念上的重大创新,人们越来越关注选择性剪接在 VSMC 基因表达调控中的作用。本文综述了选择性剪接及其调控因子如何参与产生 VSMC 可塑性中的蛋白质多样性和改变基因表达水平。此外,我们还探讨了最近在剪接调节治疗开发方面的进展如何应用于与 VSMC 相关的病理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4cca/8508619/2915e76372f6/ijms-22-10213-g001.jpg

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