Human umbilical cord mesenchymal stem cell-derived exosomal miR-146a-5p reduces microglial-mediated neuroinflammation via suppression of the IRAK1/TRAF6 signaling pathway after ischemic stroke
Zhongfei Zhang, Xiaoxiong Zou, Run Zhang, Yu Xie, Zhiming Feng, Feng Li, Jianbang Han, Haitao Sun, Qian Ouyang, Shiting Hua, Bingke Lv, Tian Hua, Zhizheng Liu, Yingqian Cai, Yuxi Zou, Yanping Tang, Xiaodan Jiang
Abstract
results demonstrated that treatment with hUMSC-Exos significantly reduced infarct volume, attenuated behavioral deficits, and ameliorated microglia activation, as measured three days post-transient brain ischemia. Furthermore, miR-146a-5p knockdown (miR-146a-5p k/d Exos) partially reversed the neuroprotective effect of hUMSC-Exos. Our mechanistic study demonstrated that miR-146a-5p in hUMSC-Exos reduces microglial-mediated neuroinflammatory response through IRAK1/TRAF6 pathway. We conclude that miR-146a-5p derived from hUMSC-Exos can attenuate microglia-mediated neuroinflammation and consequent neural deficits following ischemic stroke. These results elucidate a potential therapeutic mechanism of action of mesenchymal stem cells and provide evidence that hUMSC-Exos represent a potential cell-free therapeutic option for ischemic stroke.