Journal of Neurosurgical Sciences 2020 Feb 10

DOI: 10.23736/S0390-5616.20.04880-8

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

Enhancement of miR-16-5p on spinal cord injury-induced neuron apoptosis and inflammatory response through inactivating ERK1/2 pathway

Qian-Cheng ZHAO ¹, Zhe-Wei XU ², Qing-Ming PENG ¹, Jia-Hui ZHOU ¹, Zhi-Yue LI ¹ ✉

¹ Department of Orthopaedics, Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China; ² Department of Orthopaedics and Traumatology, Hunan Chest Hospital, Changsha, Hunan, P.R. China

BACKGROUND: To explore the effect and mechanism of miR-16-5p on neuron apoptosis and inflammatory response induced by spinal cord injury (SCI).
METHODS: Allen's weight-drop method and Basso Bcattie Bresnahan (BBB) rating scale were used to establish SCI rat model and assess locomotor function, respectively. Histopathology of SCI rats and Sham-operated rats was validated by hematoxylin and eosin (H&E) staining. After intravenous injection of miR-16-5p agomir, miR-16-5p antagomir, pcDNA3.1-Apelin-13 or negative controls into SCI rat tails, neuron apoptosis and the expression of miR-16-5p, Apelin-13, apoptotic proteins, inflammatory response-related proteins and ERK1/2 pathway-related protein were detected. Dual luciferase reporter gene assay was applied for identifying the binding between miR-16-5p and Apelin-13.
RESULTS: SCI rats had locomotor impairment with markedly edema and hemorrhage. Upregulated miR-16-5p expression and downregulated Apelin-13 expression were presented in SCI rats. Intravenous injection of miR-16-5p antagomir or/and pcDNA3.1-Apelin-13 could increase the expression of anti-apoptotic proteins (Bcl-2 and Mcl-1) and p-ERK1/2 expression while decrease the expression of pro-apoptotic proteins (cleaved caspase-3 and Bax) and inflammatory response-related proteins (TNF-α, IL-1β and IL-6). The reverse pattern was shown in rats injected with miR-16-5p agomir. MiR-16-5p targeted Apelin-13. Promotion of miR-16-5p agomir on SCI was attenuated by injection of agomir + pcDNA3.1-Apelin-13.
CONCLUSIONS: Downregulation of miR-16-5p could upregulate Apelin-13 expression to activate ERK1/2 pathway, thus alleviating SCI-induced neuron apoptosis and inflammatory response.

KEY WORDS: Spinal cord injury; miR-16-5p; Apelin-13; Apoptosis; Inflammatory response; ERK1/2 pathway; miRNA