MiR-379-5p improved locomotor function recovery after spinal cord injury in rats by reducing endothelin 1 and inhibiting astrocytes expression

J.-C. A, Z.-Y. Li, Q.-F. Long, D.-Y. Wang, H.-S. Zhao, S.-L. Jia, W.-H. Zhang

Department of Orthopedics, Qinghai Red Cross Hospital, Xining, China. spinezwh@163.com

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• Orthopedics

OBJECTIVE: The aim of this study was to investigate the effect of microRNA-214-5p (miR-214-5p) on spinal cord injury (SCI) and to explore the mechanism of action in pathophysiological relevance.
MATERIALS AND METHODS: The model of SCI was successfully established in rats aged 6-8 weeks. The levels of the locomotor function recovery in rats of the miR-379-5p group and SCI group were detected one month later by Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Biochemical indexes were measured by Western blotting and real time-PCR, respectively. In addition, rat astrocytes were cultured to verify the effect of miR-379-5p on activated astrocytes in vitro.
RESULTS: Compared with the SCI group, the rats in the miR-379-5p group showed prominent improvement in the locomotor function in vivo. MiR-379-5p attenuated the activation of astrocytes and significantly suppressed the expressions of the nerve growth inhibitors. Furthermore, the down-regulation of endothelin-1 (ET-1) ameliorated the spinal cord ischemia, thereby reducing apoptosis and oxidative stress. Compared with the pentylenetetrazol (PTZ) group, ET-1 and chondroitin sulfate poly-glycoprotein (CSPG) in miR-379-5p group decreased significantly in the astrocytes transfected with miR-214-5p in vitro.
CONCLUSIONS: MiR-379-5p retarded the neurofilament regeneration block effect by inhibiting endothelin 1 and the expression of the astrocytes after SCI. Furthermore, it might relieve nerve structure destruction, resist oxidative stress, and inhibit apoptosis, eventually promoting functional recovery.

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