Exosomal microRNA-23b-3p from bone marrow mesenchymal stem cells maintains T helper/Treg balance by downregulating the PI3k/Akt/NF-κB signaling pathway in intracranial aneurysm

Abstract

Bone marrow mesenchymal stem cells (BMSCs) are involved in cancer initiation and metastasis, and sometimes mediate cell communication by releasing exosomes and delivering microRNAs (miRNAs). The study aims to investigate the effects of exosomal hsa-miR-23b-3p derived from human BMSCs on intracranial aneurysm (IA). Firstly, human BMSCs-derived exosomes were extracted by ultra-high speed centrifugation. After clinical specimen collection, imbalance of T helper (Th) 17/Treg was found in patients with IA. Then, basilar artery aneurysm models were established and BMSCs-derived exosomes were isolated and identified. The results showed that BMSCs-derived exosomes improved pathological remodeling of IA wall, upregulated the contractile phenotype and inhibited the secretory phenotype of smooth muscle cells and reduced the number of Th17 cells to maintain the balance of Th17/Treg. In addition, human BMSCs-derived exosomes inhibited the activation of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/nuclear factor-kappa B (NF-κB) signaling pathway and maintained Th17/Treg balance, which in turn interfered with aneurysm formation. Finally, the targeting relationship between hsa-miR-23b-3p and KLF5 was confirmed. We further noted that BMSCs-derived exosomal hsa-miR-23b-3p inhibited IA formation by targeting KLF5 through suppression of the PI3k/Akt/NF-κB signaling pathway. All in all, our study concluded that BMSCs-derived exosomal hsa-miR-23b-3p could maintain Th17/Treg balance by targeting KLF5 through suppression of the PI3k/Akt/NF-κB signaling pathway, thus inhibit IA formation.