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Downregulating lncRNA PVT1 Relieves Astrocyte Overactivation Induced Neuropathic Pain Through Targeting miR-186-5p/CXCL13/CXCR5 Axis

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Abstract

Spinal cord injury (SCI) is one of the main causes leading to neuropathic pain. Here, we aim to explore the molecular mechanism and function of lncRNA PVT1 in neuropathic pain induced by SCI. The expression of lncRNA PVT1, microRNA (miR) − 186-5p was measured via quantitative reverse transcription PCR (qRT-PCR), and the activation of astrocytes (labeled by GFAP) was detected by immunohistochemistry. Western blot was conducted to detect the expression of chemokine ligand 13 (CXCL13), chemokine receptor 5 (CXCR5), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS) and glial fibrillary acidic protein (GFAP) in spinal cord injury lesions. The levels of inflammatory cytokines (including IL-1β and IL-6) and MDA in tissues were examined via Enzyme-linked immunosorbent assay (ELISA). In vitro experiments were also conducted in primary cultured astrocyte to explore the response of astrocyte to lipopolysaccharide (LPS). What’s more, the PVT1-miR-186-5p interaction was verified via the dual luciferase activity assay and RNA immunoprecipitation (RIP) assay. The results demonstrated that the levels of PVT1, CXCL13 and CXCR5 were upregulated, while miR-186-5p were decreased in SCI rats’ spinal cord and LPS-mediated astrocytes. In the SCI model, PVT1 depletion significantly alleviated neuropathic pain, astrocytic activation and reduced the expression of neuroinflammatory factors and proteins. The relevant mechanism studies confirmed that PVT1 is a competitive endogenous RNA (ceRNA) of miR-186-5p, targets and inhibits its expression and promotes the expression of CXCL13/CXCR5, while miR-186-5p targets CXCL13. In conclusion, inhibition of lncRNA PVT1 alleviates neuropathic pain in SCI rats by upregulating miR-186-5p and down-regulating CXCL13/CXCR5. The PVT1/miR-186-5p/CXCL13/CXCR5 axis can be used as a new therapeutic target for neuropathic pain.

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Data Availability

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not- for- profit sectors.

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  1. Peisong Zhang and Hanyu Sun contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, Liaocheng People’s Hospital, No. 67 Dongchang Road, Liaocheng, 252000, Shandong, China

    Peisong Zhang, Hanyu Sun & Zhengang Ji

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  1. Peisong Zhang
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Contributions

Conceived and designed the experiments: ZJ Performed the experiments: PZ, HS, Statistical analysis PZ, HS, Wrote the paper PZ, HS, ZJ. All authors read and approved the final manuscript.

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Correspondence to Zhengang Ji.

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Our study was approved by the Ethics Review Board of Liaocheng People’s Hospital.

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Zhang, P., Sun, H. & Ji, Z. Downregulating lncRNA PVT1 Relieves Astrocyte Overactivation Induced Neuropathic Pain Through Targeting miR-186-5p/CXCL13/CXCR5 Axis. Neurochem Res 46, 1457–1469 (2021). https://doi.org/10.1007/s11064-021-03287-0

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  • DOI: https://doi.org/10.1007/s11064-021-03287-0

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