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KMID : 0381120200420010077
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Genes and Genomics
2020 Volume.42 No. 1 p.77 ~ p.85
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MiR-15a attenuates peripheral nerve injury-induced neuropathic pain by targeting AKT3 to regulate autophagy
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Cai Longxue
Liu Xianfa
Guo Qicai
Huang Qi
Zhang Qiong
Cao Zuohong
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Abstract
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Objective: Aim of this study was to detect the expression of miR-15a in rats following chronic constriction injury (CCI) and to investigate the regulatory functions of miR-15a during neuropathic pain (NP) development.
Methods: CCI was performed in adult Sprague?Dawley rats to set up the rat model of neuropathic pain. MiR-15a agomir and scrambled control were delivered into the implanted catheter of rats. The mechanical allodynia and thermal hyperalgesia were assessed in both CCI- and sham-operated groups. Rat lumbar spinal cord tissues were harvested for mRNA and protein analyses. The primary spinal microglia were isolated from adult Sprague?Dawley rats and transfected with miR-15a mimics, scramble miRNA, miR-15a inhibitor or its corresponding negative control. Cell lysates were collected for mRNA and protein analyses.
Results: Compared to sham-operated group, the expression of miR-15a in CCI rats was significantly reduced, whereas neuroinflammation in spinal cord tissues was increased. Intrathecal administration of miR-15a agomir significantly attenuated CCI-induced NP and the levels of proinflammatory cytokines, including IL-6, IL-1β, and TNF-α. AKT3 was predicted and confirmed as a miR-15a-regulated gene. We further demonstrated that miR-15a overexpression downregulated the level of AKT3 in primary rat microglia and rat CCI model. Moreover, the upregulation of miR-15a induced the expressions of autophagy-associated proteins, suggesting that the regulation mechanism of miR-15a in NP development involves AKT3-mediated autophagy via inhibiting the expression of AKT3.
Conclusion: Our findings indicated that miR-15a might serve as a promising therapeutic target for the management of NP through the stimulation of autophagic process.
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KEYWORD
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AKT3, Autophagy, Chronic constriction injury, miR-15a, Neuropathic pain
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