Yu Anyong, Zhang Tianxi, Zhong Wenyi, Duan Haizhen, Wang Song, Ye Peng, Wang Juan, Zhong Shanchuan, Yang Zhao
Department of Emergency, The First Affiliated Hospital of Zunyi Medical College, Guizhou 563003, China.
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, China.
Immunol Lett. 2017 Feb;182:18-23. doi: 10.1016/j.imlet.2017.01.002. Epub 2017 Jan 3.
Autophagic activation mediated inflammation contributes to brain injury of intracerebral hemorrhage (ICH). MiRNAs play a key role in inflammation, which negatively and posttranscriptionally regulate gene expression and function. Modulating the mTOR signal, a central regulator of autophagy, could be of great significance for ICH. However, the specific of miRNA is unknown. In the current study, we detected the miRNA-144 expression, autophagic activity and inflammation of microglia in ICH. We also knocked down endogenous miRNA-144 to regulate autophagy and inflammation in ICH. In addition, we assessed the neurological damge in ICH mice. We found that ICH promoted miRNA-144 expression but downregulated mTOR expression. In addition, upregulation of mTOR attenuated microglial autophagy and inflammation in ICH. Furthermore, downregulation of miRNA-144 also inhibited inflammation, brain edema and improved neurological functions in ICH mice. Taken together, our findings suggested that miRNA-144 was a crucial regulator of autophagy via regulation of mTOR, and represented a promising therapeutical strategy for ICH.
自噬激活介导的炎症反应促成了脑出血(ICH)后的脑损伤。微小RNA(miRNAs)在炎症反应中发挥关键作用,其通过负向转录后调控基因表达及功能。调控自噬的核心调节因子——哺乳动物雷帕霉素靶蛋白(mTOR)信号,对脑出血可能具有重要意义。然而,miRNA的具体作用尚不明确。在本研究中,我们检测了脑出血后小胶质细胞中miRNA-144的表达、自噬活性及炎症反应。我们还敲低内源性miRNA-144以调控脑出血后的自噬和炎症反应。此外,我们评估了脑出血小鼠的神经损伤情况。我们发现,脑出血促进了miRNA-144的表达,但下调了mTOR的表达。此外,上调mTOR可减轻脑出血后小胶质细胞的自噬和炎症反应。此外,下调miRNA-144也可抑制脑出血小鼠的炎症反应、脑水肿,并改善其神经功能。综上所述,我们的研究结果表明,miRNA-144通过调控mTOR是自噬的关键调节因子,为脑出血提供了一种有前景的治疗策略。