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

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.