线粒体DNA(mtDNA)作为内源性激动剂,由于缺少丰富的组蛋白保护,容易在应激下受损,从而导致mtDNA片段通过多种途径被进一步释放到肿瘤微环境(TME)中,成为激活环磷酸鸟苷-腺苷合成酶(cGAS-STING)通路的关键触发因素。因此,研究设想通过治疗手段加...
实验结果显示突变LIR2基序后,在应激状态下,胞质中mtDNA进一步积累,并加剧了cGAS-STING炎症通路的激活。 TFAM介导应激状态下mtDNA的自噬途径清除进而抑制cGAS-STING通路激活 综上所述,本研究阐明了应激状态下,释放至胞质中mtDNA的清除机制,揭示了...
IL-1β使cGAS和STING的磷酸化表达量增加 HFF细胞本身高表达STING;IL-1β诱导后,STING同DNA、cGAMP处理相似,围绕在核周围变多 IRF3的激活是由TBK1和IKKε蛋白激酶介导的,它们与MAVS(线粒体病毒信号转导激活因子)、STING或TRIF(TIR-domain-containing adapter-inducing interferon-β)等衔接分子协调,以调控下游底物。
鼠伤寒诱导mtDNA释放是诱导I型IFN的重要因素。本研究阐明了细菌致病菌激活cGAS-STING通路的一种新机制,并阐明了cGAS-STING的重要作用美国。鼠伤寒感染。 重要性作为最常见的食源性人畜共患病病原体之一,美国。鼠伤寒引起人和动物的腹泻病。美国。鼠伤寒感染被认为是巨噬细胞I型干扰素(IFN)反应的诱导剂,但其机制尚...
阐述mtDNA-cGAS-STING-IRF7/3-NLRP3轴 调控巨噬细胞焦亡 改善重症急性胰腺炎肺损伤的机制 近日,首都医科大学附属北京妇产医院阴赪宏教授团队在中科院1区期刊《Cellular & Molecular Biology Letters》上发表题为“Mitochondrial (mt)DNA–cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signal...
方法:为探索RAD51抑制对TNBC细胞中c GAS-STING信号通路的影响及分子机制,首先选用小干扰RNA(si RAD51)处理以抑制人源TNBC细胞MDA-MB-231及鼠源TNBC细胞4T1中的RAD51基因表达,小分子抑制剂B02处理以抑制RAD51重组酶活性.采用Western blot法检测TNBC细胞的先天免疫c GAS-STING信号通路中c GAS,TBK1,IRF3,STING关键...
Moreover, the cGAS inhibitor RU.521 effectively attenuated NLRP3 inflammasome and S-AKI; however, these effects were abolished by treatment with the STING agonist DMXAA. Furthermore, cytosolic release of mtDNA and activation of the cGAS–STING–NLRP3 axis were observed in LPS-treated HK-2 cells...
Mechanistically, mtDNA released from TAA-stressed hepatocytes could be engulfed by macrophages, further inducing macrophage STING activation in a cGAS- and dose-dependent manner. XBP1 deficiency increased ROS production to promote hepatocellular pyroptosis by activating NLRP3/caspase-1/GSDMD signaling, ...
Double-knockout mice revealed that the effects of PINK1 on hypertrophy were dependent on STING. CONCLUSIONS. Our findings suggest that PINK1-mediated mitophagy plays a protective role in pressure overload-induced cardiac hypertrophy via inhibiting the mtDNA-cGAS-STING pathway.Cardiovascular ResearchZhou ...
阻断mPTP孔后显著抑制了胞浆mtDNA积聚.3)Western blot和透射电镜结果显示mtDNA参与了自噬的发生,RNA-seq,共聚焦结果进一步证明mtDNA通过影响cGAS-TING通路促进食管癌细胞自噬.4)靶向抑制cGAS-STING通路或清除胞浆mtDNA后,显著抑制了自噬的发生和食管癌进展.结论:本研究系统阐述了TFAM缺失介导的mtDNA应激促进食管癌发生的...