期刊
JOURNAL OF NEUROCHEMISTRY
卷 153, 期 6, 页码 710-726出版社
WILEY
DOI: 10.1111/jnc.14963
关键词
apoptosis; blood-brain barrier; microRNA-9-5p; neuroinflammation; Ptch-1; traumatic brain injury
资金
- National Natural Science Foundation of China [81571159]
- National Natural Science Foundation for Youth of China [81801230]
- Health Commission of Wuhan Municipality scientific research Funding [WX19Q17]
- Health Commission of Hubei Province scientific research project [WJ2019H364]
- Capital's Funds for Health Improvement and Research [CFH2018-2-2042]
The level of microRNA-9-5p (miRNA-9-5p) in brain tissues is significantly changed after traumatic brain injury (TBI). However, the effect of miRNA-9-5p for brain function in TBI has not been elucidated. In this study, a controlled cortical impact model was used to induce TBI in Sprague-Dawley rats, and an oxygen glucose deprivation model was used to mimic the pathological state in vitro. Brain microvascular endothelial cells (BMECs) and astrocytes were extracted from immature Sprague-Dawley rats and cocultured to reconstruct blood-brain barrier (BBB) in vitro. The results show that the level of miRNA-9-5p was significantly increased in brain tissues after TBI, and up-regulation of miRNA9-5p contributed to the recovery of neurological function. Up-regulation of miRNA-9-5p with miRNA agomir may significantly alleviate apoptosis, neuroinflammation, and BBB damage in rats after TBI. Moreover, a dual luciferase reporter assay confirmed that miRNA-9-5p is a post-transcriptional modulator of Ptch-1. In in vitro experiments, the results confirmed that up-regulation of miRNA-9-5p with miRNA mimic alleviates cellular apoptosis, inflammatory response, and BBB damage mainly by inhibiting Ptch-1. In addition, we found that the activation of Hedgehog pathway was accompanied by inhibition of NF-kappa B/MMP-9 pathway in the BMECs treated with miRNA-9-5p mimic. Taken together, these results indicate that up-regulation of miRNA-9-5p alleviates BBB damage and neuroinflammatory responses by activating the Hedgehog pathway and inhibiting NF-kappa B/MMP-9 pathway, which promotes the recovery of neurological function after TBI.
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