miR-136-5p Regulates the Inflammatory Response by Targeting the IKKß/NF-κB/A20 Pathway After Spinal Cord Injury.
Cell Physiol Biochem
; 50(2): 512-524, 2018.
Article
em En
| MEDLINE
| ID: mdl-30308489
ABSTRACT
BACKGROUND/AIMS:
miR-136-5p participates in recovery after spinal cord injury (SCI) via an unknown mechanism. We investigated the mechanism underlying the involvement of miR-136-5p in the inflammatory response in a rat model of SCI.METHODS:
Sprague-Dawley rat astrocytes were cultured in vitro to construct a reporter plasmid. Luciferase assays were used to detect the ability of miR-136-5p to target the IKKß and A20 genes. Next, recombinant lentiviral vectors were constructed, which either overexpressed miR-136-5p or inhibited its expression. The influence of miR-136-5p overexpression and miR-136-5p silencing on inflammation was observed in vivo in an SCI rat model. The expression of IL-1ß, IL-6, TNF-α, IFN-α, and related proteins (A20, IKKß, and NF-κB) was detected.RESULTS:
In vitro studies showed that luciferase activity was significantly activated in the presence of the 3' untranslated region (UTR) region of the IKKß gene after stimulation of cells with miR-136-5p. However, luciferase activity was significantly inhibited in the presence of the 3'UTR region of the A20 gene. Thus, miR-136-5p may act directly on the 3'UTR regions of the IKKß and A20 genes to regulate their expression. miR-136-5p overexpression promoted the production of related cytokines and NF-κB in SCI rats and inhibited the expression of A20 protein.CONCLUSION:
Overexpression of miR-136-5p promotes the generation of IL-1ß, IL-6, TNF-α, IFN-α, IKKß, and NF-κB in SCI rats but inhibits the expression of A20. Under these conditions, inflammatory cell infiltration into the rat spinal cord increases and injury is significantly aggravated. Silencing of miR-136-5p significantly reduces the protein expression results described after miR-136-5p overexpression and ameliorates the inflammatory cell infiltration and damage to the spinal cord. Therefore, miR-136-5p might be a new target for the treatment of SCI.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Traumatismos da Medula Espinal
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NF-kappa B
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MicroRNAs
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Proteínas de Ligação a DNA
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Quinase I-kappa B
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article