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.
Highlights
Epigenetics and RNA Biology Program Centenary Institute, The University of Sydney, Faculty of Medicine and Health, The University of Sydney, Camperdown 2050, Australia
Of mRNAs andand its its regulatory factors have been investigated in a variety of physiological and pathological regulatory factors have been investigated in a variety of physiological and pathological studies have revealed an an expanding rolerole of alternative splicing (AS)
Using scRNA-Seq analyses of DExH-box helicase 9 (DHX9)-knockdown primary vascular smooth muscle cells (VSMCs), the authors revealed that over 1000 genes were subject to AS changes, with almost 20% of these showing significant changes in gene expression regulation [19]
Summary
Physiologicalvascular vascularsmooth smoothmuscle musclecell cell plasticity vital vascular repair homeostasis. Great strides have been made to understand how transcription factors and epigestrides have been made to understand how transcription factors and epigenetics regunetics regulate phenotypic plasticity by altering gene expression. Many of these studies late phenotypic plasticity by altering gene expression. RNA biology, there has been a growing focus on co-transcriptional processes that regulate regulate gene expression in VSMCs. In particular, alternative splicing of mRNAs gene expression in VSMCs. of mRNAs andand its its regulatory factors have been investigated in a variety of physiological and pathological regulatory factors have been investigated in a variety of physiological and pathological. AS and splicing factors in promoting protein diversity and regulating gene expression in in In this thisreview, review,we wehighlight highlightthe the major findings from such works disVSMC biology. We critically evaluate the possible avenues for modulating AS in VSMCs for therapeutic benefit
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