研究动态
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长链非编码RNA Gm44206通过NLRP3/Caspase-1/GSDMD轴促进微胶质细胞炎性凋亡并加重脑缺血再灌注损伤。

LncRNA Gm44206 Promotes Microglial Pyroptosis Through NLRP3/Caspase-1/GSDMD Axis and Aggravate Cerebral Ischemia-Reperfusion Injury.

发表日期:2023 Aug 11
作者: Liangliang Yang, Yang Gao, Jinlong Huang, Hantao Yang, Puyuan Zhao, Chen Li, Zhigang Yang
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

抑制由微胶质细胞热死发炎激活引发的炎症反应可能是缓解脑缺血再灌注损伤的有效方法之一,其具体机制尚不清楚。本研究使用具有或没有氧糖剥夺/再氧化(OGD/R)或长非编码RNA(lncRNA)Gm44206敲低的BV-2微胶质细胞作为细胞模型进行体外研究。分别使用相应试剂盒和蛋白质印迹法检测乳酸脱氢酶释放和与热死相关的蛋白质水平。通过CCK8测定微胶质细胞增殖情况。酶联免疫吸附测定用于测定促炎细胞因子的水平。本研究证实了微胶质细胞热死以及NLRP3,Caspase-1,GSDMD和含有C端卡啪��-招募结构域的细胞凋亡相关斑块样蛋白(ASC)在脑缺血再灌注损伤中的参与。此外,lncRNA Gm44206的敲低能够通过NLRP3/Caspase-1/GSDMD途径缓解OGD/R诱导的微胶质细胞热死和细胞增殖抑制,从而降低包括白细胞介素(IL)-1β,IL-6, IL-18和肿瘤坏死因子-α在内的促炎细胞因子的释放。总之,本研究建立了微胶质细胞热死与脑缺血再灌注损伤的相关性,并确定了lncRNA Gm44206作为NLRP3/Caspase-1/GSDMD轴介导的微胶质细胞热死的潜在调节因子,可以被视为一个有前景的治疗靶点。
Inhibition of the inflammatory response triggered by microglial pyroptosis inflammatory activation may be one of the effective ways to alleviate cerebral ischemia-reperfusion injury, the specific mechanism of which remains unclear. In this study, BV-2 microglia with or without oxygen-glucose deprivation/reoxygenation (OGD/R) or long noncoding RNA (lncRNA) Gm44206 knockdown were used as cell models to conduct an in vitro study. Detection of lactate dehydrogenase release and pyroptosis-related protein levels was performed using a corresponding kit and western blotting, respectively. Proliferation of microglia was evaluated by CCK8 assay. Enzyme-linked immunosorbent assay was applied for measuring levels of proinflammatory cytokines. This study verified the involvement of microglial pyroptosis as well as upregulation of NLRP3, Caspase-1, GSDMD, and Apoptosis-associated Speck-like protein containing a C-terminal caspase-recruitment domain (ASC) in cerebral ischemia-reperfusion injury. Moreover, knockdown of lncRNA Gm44206 could alleviate OGD/R-induced microglial pyroptosis and cell proliferation inhibition through the NLRP3/Caspase-1/GSDMD pathway, thus decreasing the release of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-18, and tumor necrosis factor-alpha. In conclusion, this study established a correlation between microglial pyroptosis and cerebral ischemia-reperfusion injury and identified lncRNA Gm44206 as a potential regulator of NLRP3/Caspase-1/GSDMD axis-mediated microglial pyroptosis, which could be considered a promising therapeutic target.