Exosomal miR-486 derived from bone marrow mesenchymal stem cells promotes angiogenesis following cerebral ischemic injury by regulating the PTEN/Akt pathway

• Published in: Scientific reports Vol. 14; no. 1; pp. 18086 - 13
• Main Authors: Bao, Hangyang, Mao, Shihui, Hu, Xiaowei, Li, Lin, Tao, Hongmiao, Zhou, Jie, Xu, Lanxi, Fang, Yan, Zhang, Yani, Chu, Lisheng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/1647/1407; 631/1647/767; 631/337/384; 631/80/304; 631/80/84; 631/80/86; 692/699/375; AKT protein; Angiogenesis; Angiogenesis inhibitors; Animals; Bone marrow; Brain injury; Brain Ischemia - metabolism; Brain Ischemia - pathology; Cell Movement; Cell Proliferation; Disease Models, Animal; Endothelial cells; Endothelial Cells - metabolism; Exosomes; Exosomes - metabolism; Humanities and Social Sciences; Ischemia; Kinases; Male; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; Microvasculature; miRNA; Molecular modelling; multidisciplinary; Neovascularization, Physiologic; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Rats; Rats, Sprague-Dawley; Recovery of function; Science; Science (multidisciplinary); Signal Transduction; siRNA; Stem cells; Stroke; Transfection
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-69172-2

Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have been shown to promote angiogenesis after ischemic stroke, in which microRNAs (miRs) are believed to play an important role in exosome-mediated therapeutic effects, though the mechanism is still not clear. In this study, a series of molecular biological and cellular assays, both in vitro and in vivo, were performed to elucidate the role of exosomal miR-486 in angiogenesis following cerebral ischemic and its molecular mechanisms. Our results revealed that BMSC-Exos significantly improved neurological function and increased microvessel density in ischemic stroke rats. In vitro assays showed that BMSC-Exos promoted the proliferation, migration, and tube formation ability of oxygen–glucose deprivation/reoxygenation (OGD/R) injured rat brain microvascular endothelial cells (RBMECs). Importantly, BMSC-Exos increased the expression of miR-486 and phosphorylated protein kinase B (p-Akt) and down-regulated the protein level of phosphatase and tensin homolog (PTEN) in vivo and in vitro. Mechanistic studies demonstrated that transfection with miR-486 mimic enhanced RBMECs angiogenesis and increased p-Akt expression, while inhibited PTEN expression. On the other hand, the miR-486 inhibitor induced an opposite effect, which could be blocked by PTEN siRNA. It was thus concluded that exosomal miR-486 from BMSCs may enhance the functional recovery by promoting angiogenesis following cerebral ischemic injury, which might be related to its regulation of the PTEN/Akt pathway.