microRNA-26a shuttled by extracellular vesicles secreted from adipose-derived mesenchymal stem cells reduce neuronal damage through KLF9-mediated regulation of TRAF2/KLF2 axis

• Main Authors: Zixin Hou, Ji Chen, Huan Yang, Xiaoling Hu, Fengrui Yang
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2021-01-01
• Series: Adipocyte
• Subjects: adipose-derived mesenchymal stem cells; extracellular vesicles; mir-26a; klf9; traf2; klf2; neuronal damage
• Online Access: http://dx.doi.org/10.1080/21623945.2021.1938829
• ISSN: 2162-3945; 2162-397X

Extracellular vesicles (EVs) are nano-sized vesicles secreted actively by numeorus cells and have fundamental roles in intercellular communication through shuttling functional RNAs. This study sets out to elucidate the role of microRNA-26a (miR-26a) shuttled by EVs derived from adipose-derived mesenchymal stem cells (ASCs) in neuronal damage. After extraction and identification of ASC-derived EVs (ASC-EVs), mouse cortical neuronal cells were selected to establish an in vivo cerebral ischemia/reperfusion mouse model and an in vitro oxygen glucose deprivation/reperfusion (OGD/RP) cell model. The downstream genes of miR-26a were analyzed. The gain- and loss-of function of miR-26a and KLF9 was performed in mouse and cell models. Neuronal cells were subjected to co-culture with ASC-EVs and biological behaviors were detected by flow cytometry, Motic Images Plus, TTC, TUNEL staining, qRT-PCR and western blot analysis. ASC-EVs protected neuronal cells against neuronal damage following cerebral ischemia/reperfusion, which was related to transfer of miR-26a into neuronal cells. In neuronal cells, miR-26a targeted KLF9. KLF9 could suppress the expression of TRAF2 and KLF2 to facilitate neuronal damage. In vitro and in vivo results showed that miR-26a delivered by ASC-EVs inhibited neuronal damage. In summary, ASC-EVs-derived miR-26a can arrest neuronal damage by disrupting the KLF9-meidated suppression on TRAF2/KLF2 axis.