Overexpression of TUSC7 inhibits the inflammation caused by microglia activation via regulating miR-449a/PPAR-γ

• DOI: 10.1016/j.bbrc.2018.06.111
• Publication Date: 2018-07-07T22:21:07Z
• Authors: Yanbo Yu; Mengye Zhu; Yong Zhao; Mu Xu; Mizhen Qiu
• Keywords: Inflammation; 0303 health sciences; Down-Regulation; Myelitis; Cell Line; Rats; Up-Regulation; PPAR gamma; Rats, Sprague-Dawley; MicroRNAs; 03 medical and health sciences; Animals; RNA, Long Noncoding; Microglia; Spinal Cord Injuries

The aim of this study was to investigate the mechanisms of TUSC7/miR-449a/PPAR-γ axis on the inflammation induced by microglia activation.A compressive spinal cord injury (SCI) model was established. The expressions of TUSC7, miR-449a PPAR-γ, TNF-α and IL-1β in spinal cord tissues of SCI rats and HAPI cells were determined. The interaction of TUSC7 and miR-449a was tested by RIP and RNA pull-down assays. The regulatory relationship between miR-449a and PPAR-γ was tested by dual luciferase reporter gene assay.In the spinal cord tissue of SCI rats and HAPI cells induced by LPS, TUSC7 expression was reduced and miR-449a expression was increased. Overexpression of TUSC7 inhibited microglial activation and the expression of inflammatory factors (TNF-α and IL-1β). Moreover, we have found a targeting regulatory relation between TUSC7 and miR-449a, and a negative regulatory relationship between miR-449a and PPAR-γ. In the study of molecular mechanism, we found that TUSC7 could regulate PPAR-γ through miR-449a, and overexpression of TUSC7 inhibited microglial activation and the expression of inflammatory factors through miR-449a.Overexpression of TUSC7 inhibited microglial activation and the expression of inflammatory factors in microglia cells by regulating miR-449a/PPAR-γ.