Inflammatory response and apoptosis play an important role in progression of spinal cord injury (SCI). Recently, aberrant microRNAs (miRNAs) have emerged as a key regulator in SCI. However, it remains unknown whether and how miRNAs mediated the inflammatory response after SCI. The aim of this study was to evaluate the potential role of miRNAs in SCI and elucidate underlying molecular mechanisms. First, we analyzed the microRNA expression profile in spinal cords from rats following SCI, using miRNA microarray. Interestingly, miR-182-5p was one of miRNAs most significantly downregulated in SCI. It has been reported as an inflammation suppressor in different organ injury models. Here, we used a cell model to verify the regulatory function and mechanism of miR-182-5p on inflammatory response in SCI. Overexpression of miR-182-5p attenuated H2O2-induced inflammation as reflected by reduction in proinflammatory cytokines in C8-D1A cells. Meanwhile, enhanced miR-182-5p expression significantly suppressed H2O2-induced apoptosis. Toll-like receptor 4 (TLR4), an important regulator of nuclear factor kappa-B (NF-κB) signaling pathway, was identified as a novel target of miR-182-5p in C8-D1A cells. Furthermore, overexpression of TLR4 reversed inhibitory effects of miR-182-5p overexpression on inflammation and apoptosis. More importantly, we found that miR-182-5p blocked phosphorylation of nuclear p65 and promoted phosphorylation of IκB-α in H2O2-treated C8-D1A cells. Our results confirm that miR-182-5p alleviates inﬂammation and apoptosis via inactivation of TLR4/NF-κB pathway in an H2O2-induced cell model. Our findings suggest that miR-182-5p may be a potential therapeutic target of SCI in the future.
Ju M, Liu B, He H, Gu Z, Liu Y, Su Y, Zhu D, Cang J, Luo Z.Ju M, et al.Cell Cycle. 2018;17(16):2001-2018. doi: 10.1080/15384101.2018.1509635. Epub 2018 Sep 19.Cell Cycle. 2018.PMID: 30231673Free PMC article.
Nieto-Diaz M, Esteban FJ, Reigada D, Muñoz-Galdeano T, Yunta M, Caballero-López M, Navarro-Ruiz R, Del Águila A, Maza RM.Nieto-Diaz M, et al.Front Cell Neurosci. 2014 Feb 25;8:53. doi: 10.3389/fncel.2014.00053. eCollection 2014.Front Cell Neurosci. 2014.PMID: 24701199Free PMC article.Review.