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Inhibition of miR-145-5p Reduces Spinal Cord Injury-Induced Inflammatory and Oxidative Stress Responses via Affecting Nurr1-TNF-α Signaling Axis

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Abstract

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.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

SCI:

Spinal cord injury

LPS:

Lipopolysaccharide

ELISA:

Enzyme-linked immunosorbent assay

IL-1β:

Interleukin-1β

TNF-α:

Tumor necrosis factor-α

IL-6:

Interleukin-6

ROS:

Reactive oxygen species

MDA:

Malondialdehyde

GSH-Px:

Glutathione peroxidase

SOD:

Superoxide dismutase

qRT-PCR:

Quantitative real-time polymerase chain reaction

MGs:

Microglias

NF-κB:

Nuclear factor-kappa B

BBB:

Basso–Bettie–Bresnahan

3′-UTR:

3′-untranslated region

GAPDH:

Gyceraldehyde 3-phosphate dehydrogenase

miRNA:

MicroRNA

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Acknowledgements

We thank Hubei Yican Health Industry Co., Ltd. for its linguistic assistance during the preparation of this manuscript.

Author contributions

Conceived and designed the experiments: L.J.; performed the experiments: L.J., Z.-C.W., L.-L.X.; statistical analysis: L.-L.X., S.-Y.Y., C.L.; wrote the paper: L.J., Z.-C.W. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Neurosurgery, Rizhao Central Hospital, Rizhao, 276800, Shandong, China

    Lei Jiang

  2. Department of Orthopedics, Rizhao Central Hospital, Rizhao, 276800, Shandong, China

    Zeng-Chun Wei

  3. Department of ICU, Rizhao Central Hospital, Rizhao, 276800, Shandong, China

    Li-Li Xu

  4. Department of Rehabilitation Medicine, Rizhao Central Hospital, Rizhao, 276800, Shandong, China

    Shan-Ying Yu

  5. Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China

    Chao Li

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  1. Lei Jiang
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Correspondence to Lei Jiang or Chao Li.

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Jiang, L., Wei, ZC., Xu, LL. et al. Inhibition of miR-145-5p Reduces Spinal Cord Injury-Induced Inflammatory and Oxidative Stress Responses via Affecting Nurr1-TNF-α Signaling Axis. Cell Biochem Biophys 79, 791–799 (2021). https://doi.org/10.1007/s12013-021-00992-z

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