Department of rehabilitation medicine, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China.
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, 402160, China.
Sci Rep. 2017 Sep 19;7(1):11861. doi: 10.1038/s41598-017-12067-2.
Intracerebral hemorrhage promotes autophagic activation of microglia and enhances neuroinflammation. MiRNAs are key factors to autophagy, contributed to negatively and posttranscriptionally regulate gene expression and function. However, the specific miRNAs involved in the intracerebral hemorrhage mediated microglia autophagic activation are unidentified. In this experiment, microglia was treated with hemoglobin. And then, miRNA-144 expression, autophagic activation and inflammation of microglia were detected. In addition, the mTOR target of miRNA-144 and its regulation were identified. Our data demonstrated that hemoglobin promoted miRNA-144 expression and autophagic activation mediated inflammation. Additionally, miRNA-144 targeted mTOR by directly interacting with the 3' untranslated regions (UTRs), mutations of the binding sites abolish the miRNA-144 responsiveness. Overexpression of mTOR decreased autophagic activation and inflammation of microglia. Therefore, our results suggested that miRNA-144 contributed to hemoglobin mediated autophagic activation and inflammation of microglia via mTOR pathway. And miRNA based treatment provided novel therapeutical strategy for intracerebral hemorrhage.
脑出血促进小胶质细胞的自噬激活,并增强神经炎症。miRNAs 是自噬的关键因素,通过负转录后调控基因表达和功能。然而,参与脑出血介导的小胶质细胞自噬激活的特定 miRNAs 尚未确定。在这项实验中,用血红蛋白处理小胶质细胞,然后检测 microglia 的 miRNA-144 表达、自噬激活和炎症。此外,还确定了 miRNA-144 的 mTOR 靶标及其调控。我们的数据表明,血红蛋白促进了 miRNA-144 的表达,并通过直接与 3'非翻译区(UTRs)相互作用来介导炎症反应。突变结合位点可消除 miRNA-144 的反应性。mTOR 的过表达可降低小胶质细胞的自噬激活和炎症。因此,我们的结果表明,miRNA-144 通过 mTOR 通路促进了血红蛋白介导的小胶质细胞自噬激活和炎症。基于 miRNA 的治疗为脑出血提供了新的治疗策略。