MicroRNA-488 inhibits neural inflammation and apoptosis in spinal cord injury through restraint on the HMGB1/TLR4/NF-κB signaling pathway.

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  • Author(s): Niu F;Niu F; Pan S; Pan S
  • Source:
    Neuroreport [Neuroreport] 2021 Aug 11; Vol. 32 (12), pp. 1017-1026.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 9100935 Publication Model: Print Cited Medium: Internet ISSN: 1473-558X (Electronic) Linking ISSN: 09594965 NLM ISO Abbreviation: Neuroreport Subsets: MEDLINE
    • Publication Information:
      Publication: London, England : Lippincott Williams & Wilkins
      Original Publication: Oxford, UK : Rapid Communications of Oxford Ltd., [1990-
    • Subject Terms:
      Apoptosis/*physiology ; HMGB1 Protein/*metabolism ; Inflammation Mediators/*metabolism ; MicroRNAs/*metabolism ; NF-kappa B/*metabolism ; Toll-Like Receptor 4/*metabolism; Animals ; Cell Survival/physiology ; Inflammation Mediators/antagonists & inhibitors ; Male ; PC12 Cells ; Rats ; Rats, Wistar ; Signal Transduction/physiology ; Spinal Cord Injuries
    • Abstract:
      Objectives: Secondary spinal cord injury (SCI), a reversible pathological change, involves neural inflammation and apoptosis. This study explored how microRNA (miR)-488, an inflammatory regulator as reported affected secondary SCI.
      Methods: In vivo, Wistar rats were clipped on the spinal cord for SCI induction. In vitro, PC-12 cells were treated with lipopolysaccharide (LPS) to induce cell injuries to mimic the environment during the secondary SCI. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry. The levels of inflammation-related factors (interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α) in the serum and PC-12 cells were determined by ELISA. The expressions of miR-488, high mobility group box 1 (HMGB1), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, toll-like receptor 4 (TLR4), phosphorylated (p)-p65 and total-p65 in rat spinal cord or PC-12 cells were analyzed by quantitative reverse transcription PCR or western blot.
      Results: After SCI induction, rats exhibited low Basso-Beattie-Bresnahan scores, promoted the release of inflammation-related factors and downregulated miR-488. LPS treatment decreased cell viability, enhanced apoptosis and downregulated miR-488. Upregulating miR-488 neutralized LPS-induced releases of inflammation-related factors and expressions of Bax and cleaved caspase-3 and counteracted LPS-induced inhibition on Bcl-2 expression. MiR-488 directly targeted HMGB1 and miR-488 mimic decreased LPS-induced HMGB1 expression. Overexpressing HMGB1 counteracted miR-488 mimic-induced decreases in the expressions of TLR4 and p-p65 and the ratio of p-p65 to Total-p65 in LPS-treated PC-12 cells.
      Conclusion: MiR-488 inhibited neural inflammation and apoptosis in SCI via its binding with HMGB1-mediated restraint on the TLR4/NF-κB signaling pathway.
      (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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    • Accession Number:
      0 (HMGB1 Protein)
      0 (Hbp1 protein, rat)
      0 (Inflammation Mediators)
      0 (MIRN488 microRNA, rat)
      0 (MicroRNAs)
      0 (NF-kappa B)
      0 (Tlr4 protein, rat)
      0 (Toll-Like Receptor 4)
    • Publication Date:
      Date Created: 20210608 Date Completed: 20220127 Latest Revision: 20220127
    • Publication Date:
      20231215
    • Accession Number:
      10.1097/WNR.0000000000001680
    • Accession Number:
      34102644