MicroRNA-21a-5p Promotes Cerebral Angiogenesis in Transient Ischemic Attack by Targeting RBMS3 and Subsequently Modulating the TGFBR1/SMAD2/3 Pathway

IF 5 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-08-18 DOI:10.1111/cns.70573

Jiahui Wang, Yanyan Li, Jingyi Wang, Shiling Chen, Luwei Nie, Xuan Wu, Jiarui Li, Ping Zhang, Zhouping Tang

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Abstract

Aims

Transient ischemic attack (TIA) serves as a crucial precursor to a potential stroke. Angiogenesis is essential for the renovation of the damaged brain after TIA. This study aimed to elucidate the role of miRNA-21a-5p in angiogenesis following TIA and unravel the underlying mechanisms.

Methods

In vivo and in vitro TIA models were established using the modified suture middle cerebral artery occlusion and oxygen–glucose deprivation/reoxygenation methods. Differentially expressed miRNAs in the TIA group versus the control group were identified using small RNA sequencing. The putative target genes of miRNA-21a-5p were predicted via bioinformatics analysis and validated using a dual luciferase reporter gene assay. TIA models were then treated with miRNA-21a-5p antagomir/agomir or/and an adeno-associated virus interfering with the target gene to assess the effects of miRNA-21a-5p and the identified target gene on angiogenesis after TIA.

Results

MiRNA-21a-5p was the miRNA with the most significant changes after TIA. RBMS3 was identified as a target gene for miRNA-21a-5p. Downregulation of miRNA-21a-5p expression reduced angiogenesis in animal and cellular models of TIA, and miRNA-21a-5p upregulation had a completely opposite effect. RBMS3 suppression reversed miRNA-21a-5p knockdown-mediated inhibition of angiogenesis in TIA models. Moreover, the TGFBR1/SMAD2/3 pathway was found to be downstream for miRNA-21a-5p/RBMS3.

Conclusion

MiRNA-21a-5p conferred neuroprotective effects against TIA by enhancing angiogenesis through the RBMS3/TGFBR1/SMAD2/3 pathway.

Abstract Image

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MicroRNA-21a-5p通过靶向RBMS3并随后调节TGFBR1/SMAD2/3通路促进短暂性脑缺血发作中的脑血管生成

目的短暂性脑缺血发作（TIA）是潜在中风的重要前兆。血管生成对于TIA后受损大脑的修复至关重要。本研究旨在阐明miRNA-21a-5p在TIA后血管生成中的作用并揭示其潜在机制。方法采用改良缝合大脑中动脉闭塞法和氧葡萄糖剥夺/再氧合法建立TIA模型。使用小RNA测序鉴定TIA组与对照组差异表达的mirna。通过生物信息学分析预测了miRNA-21a-5p的假定靶基因，并使用双荧光素酶报告基因试验进行了验证。然后用miRNA-21a-5p / agagomir或/和干扰靶基因的腺相关病毒治疗TIA模型，以评估miRNA-21a-5p和鉴定的靶基因对TIA后血管生成的影响。结果TIA后变化最显著的miRNA是miRNA -21a-5p。RBMS3被鉴定为miRNA-21a-5p的靶基因。在TIA动物和细胞模型中，miRNA-21a-5p表达下调可减少血管生成，而miRNA-21a-5p表达上调则具有完全相反的作用。RBMS3抑制逆转了TIA模型中miRNA-21a-5p敲低介导的血管生成抑制。此外，TGFBR1/SMAD2/3通路位于miRNA-21a-5p/RBMS3的下游。结论MiRNA-21a-5p通过RBMS3/TGFBR1/SMAD2/3通路促进血管生成，对TIA具有神经保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.