Bone marrow mesenchymal stem cells-derived exosomal microRNA-124-3p attenuates hypoxic-ischemic brain damage through depressing tumor necrosis factor receptor associated factor 6 in newborn rats

• Published in: Bioengineered Vol. 13; no. 2; pp. 3195 - 3207
• Main Authors: Min, Weijie, Wu, Yina, Fang, Yibin, Hong, Bo, Dai, Dongwei, Zhou, Yu, Liu, Jianmin, Li, Qiang
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.02.2022
• Subjects: Animals; Bone Marrow Cells - metabolism; bone marrow mesenchymal stem cells; Brain Injuries - metabolism; Brain Injuries - therapy; Brain Ischemia - metabolism; Brain Ischemia - therapy; exosomes; Exosomes - metabolism; Exosomes - transplantation; Hypoxic-ischemic brain damage; Male; Mesenchymal Stem Cells - metabolism; MicroRNA-124-3p; MicroRNAs - metabolism; Rats; Rats, Sprague-Dawley; Research Paper; TNF Receptor-Associated Factor 6 - metabolism; tumor necrosis factor receptor associated factor 6; MicroRNA-124-3p; bone marrow mesenchymal stem cells; Hypoxic-ischemic brain damage; exosomes; tumor necrosis factor receptor associated factor 6
• ISSN: 2165-5979; 2165-5987; 2165-5987
• DOI: 10.1080/21655979.2021.2016094

Mesenchymal stem cells (MSCs)-derived exosomes (Exo) are beneficial in the use of brain damages. Restrictively, the mechanism of Exo expressing miR-124-3p in hypoxic-ischemic brain damage (HIBD) is not completely comprehended. Thereupon, this work was put forward to reveal the action of bone marrow MSCs-derived Exo (BMSCs-Exo) expressing miR-124-3p in the illness. BMSCs were isolated and transfected with miR-124-3p agomir. Then, BMSCs-Exo were extracted and identified. The newborn HIBD rats were injected with miR-124-3p-modified BMSCs-Exo or tumor necrosis factor receptor associated factor 6 (TRAF6)-related vectors. Next, neurological functions, neuron pathological and structural damages, oxidative stress and neuronal apoptosis were observed. miR-124-3p and TRAF6 expression was tested, along with their targeting relationship. miR-124-3p was down-regulated, and TRAF6 was up-regulated in newborn HIBD rats. miR-124-3p targeted TRAF6. BMSCs-Exo improved neurological functions, alleviated neuron pathological and structural damages, suppressed oxidative stress and reduced neuronal apoptosis in newborn HIBD rats, whereas BMSCs-Exo-mediated effects were enhanced by restoring miR-124-3p. Silencing TRAF6 attenuated HIBD in newborn rats, but overexpression of TRAF6 reversed the protective role of miR-124-3p-overexpressing BMSCs-Exo. This work makes it comprehensive that up-regulated exosomal miR-124-3p ameliorates HIBD in newborn rats by targeting TRAF6, which replenishes the potential agents for curing HIBD.