• Neuroscience · Aug 2020

    Upregulation of miRNA-9-5p promotes angiogenesis after traumatic brain injury by inhibiting Ptch-1.

    • Jingchuan Wu, Junchi He, Xiaocui Tian, Hui Li, Yi Wen, Qiang Shao, Chongjie Cheng, Guangyu Wang, and Xiaochuan Sun.
    • Department of Neurosurgery, General Hospital of The YangTze River Shipping, Wuhan Brain Hospital, Wuhan, Hubei 430014, China; Department of Neurosurgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
    • Neuroscience. 2020 Aug 1; 440: 160-174.

    AbstractMicroRNA-9-5p (miRNA-9-5p) is an important regulator of angiogenesis in many pathological states. However, the effect of miRNA-9-5p on angiogenesis after traumatic brain injury (TBI) has not been elucidated. In this study, a controlled cortical impact (CCI) model was used to induce TBI in Sprague-Dawley rats, and an oxygen glucose deprivation (OGD) model was used to mimic the pathological state in vitro. Brain microvascular endothelial cells (BMECs) were extracted from immature rats. The results showed that the level of miRNA-9-5p was significantly increased in the traumatic foci after TBI, and the upregulation of miRNA9-5p promoted the recovery of neurological function. Moreover, the upregulation of miRNA-9-5p with miRNA agomir significantly increased the density of the microvascular and neurons around the traumatic foci in rats after TBI. The results of the in vitro experiments confirmed that the upregulation of miRNA-9-5p with a miRNA mimic improved cellular viability and alleviated cellular apoptosis. Dual luciferase reporter assay validated that miRNA-9-5p was a posttranscriptional modulator of Ptch-1. Activation of the Hedgehog pathway by increasing the level of miRNA-9-5p promoted the migration and tube formation of BMECs in vitro. In addition, we found that the upregulation of miRNA-9-5p activated the Hedgehog pathway and increased the phosphorylation of AKT, which promoted the expression of cyclin D1, MMP-9 and VEGF in BMECs. All these results indicate that the upregulation of miRNA-9-5p promotes angiogenesis and improves neurological functional recovery after TBI, mainly by activating the Hedgehog pathway. MiRNA-9-5p may be a potential new therapeutic target for TBI.Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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