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Downregulation of miR-199b promotes the acute spinal cord injury through IKKβ-NF-κB signaling pathway activating microglial cells
Abstract
Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and IκB kinase β-nuclear factor-kappa B (IKKβ-NF-κB) signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of IKKβ/NF-κB were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKKβ by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKKβ, p-p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-α and IL-1β. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKKβ-NF-κB signaling pathway and TNF-α and IL-1β. These results indicated that miR-199b attenuated ASCI at least partly through IKKβ-NF-κB signaling pathway and affecting the function of microglia. Our findings sug…
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“BV2 cells were employed extensively to induce cell injuries, emulating an in vitro model of SCI [36].”
From miR-223 accelerates lipid droplets clearance in microglia following spinal cord injury by upregulating ABCA1 (2024) · cites this paper as [36]
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Cited by
Sorted by citations
Liu, Z., Yao, X., Jiang, W., Li, W., Zhu, S., Liao, C., Zou, L., Ding, R., & Chen, J. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01751-2 · Cited by 430
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Self-citation
Metadata
- Authors
- Zhou, H.-J., Wang, L.-Q., Xu, Q.-S., Fan, Z.-X., Zhu, Y., Jiang, H., Zheng, X.-J., Ma, Y.-H., & Zhan, R.-Y.
- Venue
- Experimental Cell Research
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 349
- Issue
- 1
- Pages
- 60-67
- ISSN
- 0014-4827
- Cited by
- 64
- References
- 3
- Language
- en
- Funders
- National Natural Science Foundation of China (81371371)
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- Zhou, H.-J., Wang, L.-Q., Xu, Q.-S., Fan, Z.-X., Zhu, Y., Jiang, H., Zheng, X.-J., Ma, Y.-H., & Zhan, R.-Y. (2016). Downregulation of miR-199b promotes the acute spinal cord injury through IKKβ-NF-κB signaling pathway activating microglial cells. Experimental Cell Research. https://doi.org/10.1016/j.yexcr.2016.09.020