Inhibition of miR-145-5p Reduces Spinal Cord Injury-Induced Inflammatory and Oxidative Stress Responses via Affecting Nurr1-TNF-α Signaling Axis
Autor: | Chao Li, Zeng-Chun Wei, Li-Li Xu, Shan-Ying Yu, Lei Jiang |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Biophysics Inflammation Pharmacology medicine.disease_cause Biochemistry Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound medicine chemistry.chemical_classification Reactive oxygen species 030102 biochemistry & molecular biology biology Tumor Necrosis Factor-alpha Glutathione peroxidase Cell Biology General Medicine Malondialdehyde Blot 030104 developmental biology chemistry biology.protein Tumor necrosis factor alpha medicine.symptom Oxidative stress |
Zdroj: | Cell Biochemistry and Biophysics. 79:791-799 |
ISSN: | 1559-0283 1085-9195 |
Popis: | Inflammation and oxidative stress feature prominently in the secondary spinal cord injury (SCI). The present work is targeted at deciphering miR-145-5p's role and underlying mechanism in SCI. We randomly divided Sprague-Dawley rats into SCI group and control group. Microglial BV2 cells were separated into control group and lipopolysaccharide (LPS) treatment group. Enzyme-linked immunosorbent assay was carried out for determining the concentrations of interleukin-6, interleukin-1β, and tumor necrosis factor-α (TNF-α). The expressions of malondialdehyde, glutathione peroxidase, superoxide dismutase, and reactive oxygen species were also detected. TNF-α, miR-145-5p, and Nurr1 expressions were examined by western blot and quantitative real-time polymerase chain reaction. Western blotting and dual-luciferase reporter gene assay were conducted to examine the regulating impact that miR-145-5p had on Nurr1 and TNF-α. MiR-145-5p was remarkably upregulated in the SCI rat model's spinal cord tissues and BV2 cells treated with LPS, and Nurr1 expression was dramatically lowered. Furthermore, miR-145-5p inhibition markedly repressed inflammatory and oxidative stress responses. Moreover, it was proved that Nurr1 was a direct miR-145-5p target. The inhibition of miR-145-5p helped promote Nurr1 expression to block TNF-α signaling. MiR-145-5p inhibition mitigates inflammation and oxidative stress via targeting Nurr1 to regulate TNF-α signaling, which ameliorates SCI. |
Databáze: | OpenAIRE |
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