期刊
JOURNAL OF NEUROTRAUMA
卷 39, 期 9-10, 页码 701-714出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/neu.2021.0290
关键词
apoptosis; exosomes; hypoxic condition; miRNA; oxygen-glucose deprivation and reperfusion; spinal cord injury
资金
- National Key RAMP
- D Program of China [2019YFA0112100]
- National Natural Science Foundation of China [81472073]
- Natural Science Foundation of Hunan Province [2019JJ40518]
Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy using adipose tissue-derived stromal cell-secreted exosomes can reduce neuronal apoptosis and promote functional recovery after SCI.
Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy has become a novel strategy for tissue injury repair. We designed a method to treat SCI using exosomes secreted by adipose tissue-derived stromal cells (ADSCs) under hypoxic conditions. We established a neuronal oxygen-glucose deprivation and reperfusion (OGD/R) model in vitro to simulate the hypoxic environment after SCI. We observed that exosomes derived from hypoxia-conditioned ADSCs (Hypo-exo) significantly reduced neuronal apoptosis after OGD. By establishing a rat SCI model, we found that Hypo-exo can significantly reduce the formation of cavities in the injured area and improve the functional recovery of the hindlimbs of rats after injury. To explore the molecular mechanism, we conducted microRNA sequencing analysis of exosomes. Through real-time polymerase chain reaction, dual luciferase reporter assays and signaling pathway chip analysis, we determined that miR-499a-5p regulates the JNK3/c-jun-apoptotic signaling pathway by targeting JNK3. Further, we verified the expression of the key proteins in the JNK3/c-jun-apoptotic signaling pathway by immunofluorescence and Western blotting. These results support the hypothesis that Hypo-exo can reduce neuronal apoptosis after SCI and may provide new methods to treat SCI.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据