TUSC7 的过表达通过调控 miR-449a/PPAR-γ 抑制小胶质细胞激活引起的炎症。
Overexpression of TUSC7 inhibits the inflammation caused by microglia activation via regulating miR-449a/PPAR-γ.
机构信息
Department of Pain, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Department of Pain, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
出版信息
Biochem Biophys Res Commun. 2018 Sep 5;503(2):1020-1026. doi: 10.1016/j.bbrc.2018.06.111. Epub 2018 Jul 7.
OBJECTIVE
The aim of this study was to investigate the mechanisms of TUSC7/miR-449a/PPAR-γ axis on the inflammation induced by microglia activation.
METHODS
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.
RESULTS
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.
CONCLUSION
Overexpression of TUSC7 inhibited microglial activation and the expression of inflammatory factors in microglia cells by regulating miR-449a/PPAR-γ.
目的
本研究旨在探讨 TUSC7/miR-449a/PPAR-γ 轴在小胶质细胞激活诱导炎症反应中的作用机制。
方法
建立压迫性脊髓损伤（SCI）模型。测定 SCI 大鼠脊髓组织和 HAPI 细胞中 TUSC7、miR-449a、PPAR-γ、TNF-α 和 IL-1β 的表达。通过 RIP 和 RNA 下拉实验检测 TUSC7 与 miR-449a 的相互作用。通过双荧光素酶报告基因实验检测 miR-449a 与 PPAR-γ 的调控关系。
结果
在 LPS 诱导的 SCI 大鼠脊髓组织和 HAPI 细胞中，TUSC7 表达降低，miR-449a 表达升高。过表达 TUSC7 抑制小胶质细胞激活和炎症因子（TNF-α 和 IL-1β）的表达。此外，我们发现 TUSC7 与 miR-449a 之间存在靶向调节关系，miR-449a 与 PPAR-γ 之间存在负向调节关系。在分子机制研究中，我们发现 TUSC7 可以通过 miR-449a 调节 PPAR-γ，过表达 TUSC7 可以通过 miR-449a 抑制小胶质细胞激活和炎症因子的表达。
结论
过表达 TUSC7 通过调节 miR-449a/PPAR-γ 抑制小胶质细胞激活和炎症因子的表达。
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