Long noncoding RNA MALAT1 contributes to inflammatory response of microglia following spinal cord injury via the modulation of a miR-199b/IKKβ/NF-κB signaling pathway
| Autor: | Yu Zhu, Jianbo Yu, Qing-Sheng Xu, Xiu-Jue Zheng, Li-Qing Wang, Renya Zhan, Duan-Bu Wang, Heng-Jun Zhou |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Physiology Inflammatory response Interleukin-1beta Down-Regulation Rats Sprague-Dawley Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Spinal cord injury Cells Cultured Spinal Cord Injuries Inflammation MALAT1 Lung Microglia Tumor Necrosis Factor-alpha business.industry NF-kappa B Cell Biology medicine.disease Long non-coding RNA I-kappa B Kinase Rats Nf κb signaling MicroRNAs 030104 developmental biology medicine.anatomical_structure Cancer research Cytokines Adenocarcinoma RNA Long Noncoding business Locomotion 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 315:C52-C61 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00278.2017 |
| Popis: | Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was widely recognized to be implicated in human cancer, vascular diseases, and neurological disorders. This study was to explore the role and underlying mechanism of MALAT1 in acute spinal cord injury (ASCI). ASCI models in adult rats were established and demonstrated by a numerical decrease in BBB scores. Expression profile of MALAT1 and miR-199b following ASCI in rats and in vitro was determined using quantitative real-time PCR. RNA pull-down assays combined with RIP assays were performed to explore the interaction between MALAT1 and miR-199b. In the present study, MALAT1 expression was significantly increased (2.4-fold that of control) in the spinal cord of the rat contusion epicenter accompanied by activation of IKKβ/NF-κB signaling pathway and an increase in the level of proinflammatory cytokines TNF-α and IL-1β. Upon treatment with LPS, MALAT1 expression dramatically increased in the microglia in vitro, but knockdown of MALAT1 attenuated LPS-induced activation of MGs and TNF-α and IL-1β production. Next, we confirmed that LPS-induced MALAT1 activated IKKβ/NF-κB signaling pathway and promoted the production of proinflammatory cytokines TNF-α and IL-1β through downregulating miR-199b. More importantly, MALAT1 knockdown gradually improved the hindlimb locomotor activity of ASCI rats as well as inhibited TNF-α, IL-1β levels, and Iba-1 protein, the marker of activated microglia in injured spinal cords. Our study demonstrated that MALAT1 was dysregulated in ASCI rats and in LPS-activated MGs, and MALAT1 knockdown was expected to attenuate ASCI through repressing inflammatory response of MGs. |
| Databáze: | OpenAIRE |
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