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| 1 | The essential adaptors of innate immune signaling显示文摘Microbial components and the endogenous molecules released from damaged cells can stimulate germ-line-encoded pattern recognition receptors(PRRs)to transduce signals to the hub of the innate immune signaling network-the adaptor proteins MyD88/TRIF/MAVS/STING/Caspase-1,where integrated signals relay to the relevant transcription factors IRF3/IRF7/NF-κB/AP-1 and the signal transducer and activator of tran-scription 6(STAT6)to trigger the expression of typeІinterferons and inflammatory cytokines or the assem-bly of inflammasomes.Most pleiotropic cytokines are secreted and bind to specific receptors,activating the signaling pathways including JAK-STAT for the prolif-eration,differentiation and functional capacity of im-mune cells.This review focuses on several critical adaptors in innate immune signaling cascades and recent progress in their molecular mechanisms. | Huihui Chen Zhengfan Jiang | 2013 | Protein & Cell2013，4，1： | 26 |
| 2 | The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy显示文摘The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure,myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns(mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism.Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases. | Patrick Kwabena Oduro Xianxian Zheng Jinna Wei Yanze Yang Yuefei Wang Han Zhang Erwei Liu Xiumei Gao Mei Du Qilong Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 18 |
| 3 | SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer显示文摘SIRT7,a sirtuin family member implicated in aging and disease,is a regulator of metabolism and stress responses.It remains elusive how human somatic stem cell populations might be impacted by SIRT7.Here,we found that SIRT7 expression declines during human mesenchymal stem cell(hMSC)aging and that SIRT7 deficiency accelerates senescence.Mechanistically,SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins,thus maintaining the repressive state of heterochromatin at nuclear periphery.Accordingly,deficiency of SIRT7 results in loss of heterochromatin,derepression of the LINE1 retrotransposon(LINE1),and activation of innate immune signaling via the cGAS-STING pathway.These agingassociated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor.Together,these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging. | Shijia Bi Zunpeng Liu Zeming Wu Zehua Wang Xiaoqian Liu Si Wang Jie Ren Yan Yao Weiqi Zhang Moshi Song Guang-Hui Liu Jing Qu | 2020 | Protein & Cell2020，11，7： | 10 |
| 4 | STING在宿主天然免疫信号通路中的调节作用显示文摘STING(stimulator of interferon genes)是天然免疫信号通路中一种新发现的蛋白质,在防御病毒及胞内细菌感染、介导Ⅰ型IFN产生过程中发挥重要功能.来自病原体的B型DNA与5′-3p dsRNA暴露在宿主细胞中后被相应的模式识别受体识别,通过不同的通路传递信号给STING.STING随后通过相似的机制招募TBK1激活IRF3,诱导干扰素表达.对细菌中的环二核苷酸c-di-GMP和c-di-AMP,STING则可以直接作为模式识别受体引发Ⅰ型干扰素反应.此外STING还能激活STAT6诱导特异趋化因子产生,吸引各种免疫细胞抵抗病毒感染.本文通过对STING的发现、结构、定位、功能、机理以及调节机制进行综述,以期为揭示病毒逃逸天然免疫调节机制和抗病毒新型免疫调节剂提供新的思路. | 郑洋 邢雅玲 陈晓娟 杨星星 王凯 陈忠斌 | 2013 | 生物化学与生物物理进展2013，40，1： | 9 |
| 5 | An active damping vibration control system for wind tunnel models显示文摘In wind tunnels, long cantilever sting support systems with low structural damping encounter flow separation and turbulence during wind tunnel tests, which results in destructive low-frequency and big-amplitude resonance, leading to data quality degradation and test envelope limitation. To ensure planed test envelope and obtain high-quality data, an active damping vibration control system independent of balance signal based on stackable piezoelectric actuators and velocity feedback using accelerometer, is proposed to improve the support stability and wind tunnel testing safety in transonic wind tunnel. Meanwhile, a design of powerful sting-root embedded active damping device is given and an active vibration control method is presented based on the mechanism analysis of aircraft model vibration. Furthermore, a self-adaptive fuzzy Proportion Differentiation(PD) control model is proposed to realize control parameters adjustment automatically for various testing conditions. Besides, verification tests are performed in laboratory and a continuous transonic wind tunnel. Experimental results indicate that the aircraft model does not vibrate obviously from -4° to 11° at Ma = 0.6, the number of useable angle-of-attack has increased by 7° at Ma = 0.6 and 5° at Ma = 0.7 respectively, satisfying the requirements of practical wind tunnel tests. | Wei LIU Mengde ZHOU Zhengquan WEN Zhuang YAO Yu LIU Shihong WANG Xiaochun CUI Xiao LI Bing LIANG Zhenyuan JIA | 2019 | Chinese Journal of Aeronautics2019，32，9： | 8 |
| 6 | Magnetic resonance imaging correlates of bee sting induced multiple organ dysfunction syndrome: A case report显示文摘Occasionally systemic complications with high risk of death,such as multiple organ dysfunction syndrome(MODS),can occur following multiple bee stings.This case study reports a patient who presented with MODS,i.e.,acute kidney injury,hepatic and cardiac dysfunc-tion,after multiple bee stings.The standard clinical findings were then correlated with magnetic resonance imaging(MRI)findings,which demonstrates that MRI may be utilized as a simpler tool to use than other mul-tiple diagnostics. | Sushant K Das Li-Chuan Zeng Bing Li Xiang-Ke Niu Jing-Liang Wang Anup Bhetuwal Han-Feng Yang | 2014 | World Journal of Radiology2014，6，9： | 5 |
| 7 | Allosteric inhibition reveals SHP2-mediated tumor immunosuppression in colon cancer by single-cell transcriptomics显示文摘Colorectal cancer(CRC), a malignant tumor worldwide consists of microsatellite instability(MSI) and stable(MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing wasperformed to explore the role of SHP2 in all cell types of tumor microenvironment(TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68;macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively,our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy. | Jian Gao Zhigui Wu Mingxia Zhao Rui Zhang Manru Li Dongdong Sun Haibo Cheng Xianjia Qi Yuxian Shen Qiang Xu Hongqi Chen Dijun Chen Yang Sun | 2022 | Acta Pharmaceutica Sinica B2022，12，1： | 5 |
| 8 | 炎症性肠病中cGAS-cGAMP-STING识别病原体DNA的研究进展显示文摘生物体对病原微生物核酸(包括DNA与RNA)的识别是启动宿主免疫应答的重要途径.炎症性肠病中,机体对病原体核酸的识别异常是其病因与特征之一.近年来,针对RNA的识别机制以及相关分子学基础已愈加深入,而关于DNA如何激活胞内DNA受体并调控抗原提呈细胞的功能,进而介导黏膜免疫应答却罕有研究.本综述将首先介绍肠道树突状细胞的亚群与功能,探讨树突状细胞利用cGAS-cGAMP-STING识别外源性DNA的机制,进而鉴别炎症性肠病中与DNA识别异常高度相关的易感基因. | 刘颂 任建安 | 2015 | 国际外科学杂志2015，42，7： | 4 |
| 9 | cGAS-cGAMP-STING信号通路研究进展显示文摘天然免疫是机体抵御病原体感染的第一道防线。近年来,胞质DNA受体识别外源DNA的机制及DNA病毒诱导的Ⅰ型干扰素激活过程的研究进展迅速。胞内的DNA受体c GAS(cyclic GMP-AMP synthase,c GAS)识别胞质DNA后,产生第二信使c GAMP(cyclic GMP-AMP,c GAMP),随后c GAMP与接头蛋白STING(stimulator of interferon,STING)结合并激活Ⅰ型干扰素信号通路。机体抵抗DNA病毒感染主要依赖c GAS-c GAMP-STING介导的Ⅰ型干扰素信号通路。对该信号通路的研究,不仅有助于我们加深对病原体感染引起的Ⅰ型干扰素信号转导过程的理解,并为自身免疫性疾病以及肿瘤免疫的药物设计提供理论基础。 | 吴晓霞 吕颂雅 | 2018 | 生物化工2018，4，3： | 4 |
| 10 | 急性运动对血清游离mtDNA以及先天免疫信号通路的影响显示文摘目的:探讨不同强度急性运动对小鼠外周血液循环中游离mtDNA含量和骨骼肌免疫信号通路的影响。方法:32只7周龄雄性小鼠随机分为4组:安静组(SED,n=8),低强度运动组(R10,n=8),中强度运动组(R15,n=8),高强度运动组(R20,n=8)。分别按照10 m/min、15 m/min、20 m/min的速度进行一次40 min的跑台运动,运动后即刻采集血液和腓肠肌,应用PCR技术检测小鼠血清mtDNA含量及骨骼肌免疫信号分子基因表达。结果:1)高强度运动使小鼠血清游离mtDNA含量显著增加(P<0.05),但中、低强度运动组小鼠血清游离mtDNA与安静组无显著性差异;2)中低强度运动可使线粒体相关免疫信号分子(AIM2、NLRP3、TLR9、STING、MAVS)表达增加,其中,低强度运动组AIM2和STING的表达存在显著性差异,而中等强度运动组均存在显著性差异(P<0.05),但高强度运动组免疫信号分子表达均下降,TLR9的表达存在显著性差异。结论:1)急性高强度运动可使血清游离mtDNA显著提高,并抑制先天性免疫反应,但血清游离mtDNA的来源是否来自骨骼肌尚需进一步实验证明;2)中、低强度急性运动对血清游离mtDNA含量无显著性影响,但可提高机体的先天性免疫能力,原因可能是细胞内游离mtDNA含量的增加。 | 李省天 漆正堂 丁树哲 | 2018 | 中国体育科技2018，54，1： | 4 |
| 11 | 激活Sting信号通路对GL261小鼠肿瘤模型远隔免疫效应影响显示文摘目的放疗过程中受照射病灶以外其他部位病灶消退的现象称为远隔效应,远隔效应的机制主要与免疫相关,干扰素刺激因子(stimulator of interferon genes,Sting)信号通路的激活在放疗引起免疫效应机制中起着非常重要的作用。但Sting信号通路的激活对诱发远隔效应的作用尚不明确。本研究探讨不同照射剂量对GL261小鼠胶质瘤模型Sting信号通路的激活,以及激活的Sting信号通路对原发及远隔部位肿瘤微环境中抗肿瘤免疫效应的影响。方法细胞实验:予GL261细胞系0、8和20Gy X射线照射后培养24h收集细胞,实时荧光定量PCR(quantitative real-time PCR,RT-PCR)检测免疫相关因子Sting和干扰素b(interferon-b,IFNb)的表达水平;蛋白质印迹法检测GL261细胞系Sting蛋白的表达变化。体内实验:构建小鼠两侧背部肿瘤模型,令各组别小鼠的一侧肿瘤达150mm^3,分别接受0、8和20Gy的X射线照射,照射后第5日处死小鼠并取肿瘤组织。蛋白质印迹法检测接受照射的原位肿瘤及远隔肿瘤组织内Sting蛋白表达水平,并利用ELISA试剂盒检测原位及远隔肿瘤组织中IFNb蛋白表达水平,最后通过流式细胞术检测原位及远隔肿瘤组织微环境内树突状细胞(dendritic cells,DC)及效应T(CD8a+T)细胞浸润情况。结果在体外细胞水平研究中,RT-PCR检测发现,8和20Gy照射后细胞内Sting表达较0Gy组呈增加趋势,P>0.05;8和20Gy照射后IFNb表达量分别为4.01±0.16、4.19±0.44,较对照组增加,F=39.751,P<0.001。蛋白质印迹结果提示,8、20Gy照射后细胞内Sting蛋白表达量分别为1.53±0.12、2.31±0.03,均较对照组增加,F=74.835,P<0.001。在体内小鼠动物模型研究中,蛋白质印迹检测发现,8Gy照射组原位组织(1.99±0.11)及远隔组织(1.36±0.05)中Sting蛋白表达量均较对照组增加,P值分别为<0.001和0.002;20Gy照射组原位(0.347±0.006)及远隔组织(0.177±0.008)Sting蛋白表达较对照组减少,均P<0.001。进一步使用ELISA试剂盒检测发现,仅8Gy照射组小鼠原位肿瘤组织中IFNb蛋白表达〔(111.74±13.96)pg/mL〕较对照组〔(68.84±2.40)pg/mL〕增高,F=4.345,P<0.05。流式细胞术检测发现,8Gy照射组小鼠原位肿瘤组织中DC〔(3.48±0.43)%〕及CD8a+T〔(5.28±0.77)%〕细胞浸润量均较对照组增加,F=6.793,P<0.05;而20Gy照射组原位肿瘤组织中DC及CD8a+T细胞浸润较对照组差异无统计学意义,P>0.05。结论 8Gy X射线照射能激活GL261小鼠模型中的Sting信号通路,促进免疫相关因子的表达,最终通过引起原位及远隔部位肿瘤组织中DC、CD8a+T细胞浸润增加达到增强其抗肿瘤免疫的作用。 | 方婷婷 汪步海 | 2019 | 中华肿瘤防治杂志2019，26，6： | 4 |
| 12 | cGAS-STING信号通路:免疫监视的重要机制显示文摘免疫系统识别病原微生物的主要机制之一是识别其核酸。环磷酸鸟苷-腺苷合成酶(cGAS)是一种胞质DNA感受器,感知病原DNA后激活cGAS-STING通路。该通路不仅介导天然免疫应答以抵抗多种含DNA的病原微生物感染,还能感知肿瘤来源的DNA而产生抗肿瘤免疫应答。然而,自体DNA对cGAS-STING通路的异常激活也会导致自身免疫性和炎症性疾病。本文综述了cGAS-STING信号通路及其在抗病毒天然免疫中的调控作用与功能,阐述了cGAS-STING通路在抗病毒感染和疾病中发挥的作用。 | 周萍萍 王涛 孙元 仇华吉 | 2021 | 微生物学报2021，61，7： | 4 |
| 13 | Impact of intracellular innate immune receptors on immunometabolism显示文摘Immunometabolism,which is the metabolic reprogramming of anaerobic glycolysis,oxidative phosphorylation,and metabolite synthesis upon immune cell activation,has gained importance as a regulator of the homeostasis,activation,proliferation,and differentiation of innate and adaptive immune cell subsets that function as key factors in immunity.Metabolic changes in epithelial and other stromal cells in response to different stimulatory signals are also crucial in infection,inflammation,cancer,autoimmune diseases,and metabolic disorders.The crosstalk between the PI3K-AKT-mTOR and LKB1-AMPK signaling pathways is critical for modulating both immune and nonimmune cell metabolism.The bidirectional interaction between immune cells and metabolism is a topic of intense study.Toll-like receptors(TLRs),cytokine receptors,and T and B cell receptors have been shown to activate multiple downstream metabolic pathways.However,how intracellular innate immune sensors/receptors intersect with metabolic pathways is less well understood.The goal of this review is to examine the link between immunometabolism and the functions of several intracellular innate immune sensors or receptors,such as nucleotide-binding and leucine-rich repeat-containing receptors(NLRs,or NOD-like receptors),absent in melanoma 2(AIM2)-like receptors(ALRs),and the cyclic dinucleotide receptor stimulator of interferon genes(STING).We will focus on recent advances and describe the impact of these intracellular innate immune receptors on multiple metabolic pathways.Whenever appropriate,this review will provide a brief contextual connection to pathogenic infections,autoimmune diseases,cancers,metabolic disorders,and/or inflammatory bowel diseases. | Wei-Chun Chou Elena Rampanelli Xin Li Jenny P-Y.Ting | 2022 | Cellular & Molecular Immunology2022，19，3： | 4 |
| 14 | STING inhibitor ameliorates LPS-induced ALI by preventing vascular endothelial cells-mediated immune cells chemotaxis and adhesion显示文摘Acute lung injury(ALI)is a common and devastating clinical disorder featured by excessive inflammatory responses.Stimulator of interferon genes(STING)is an indispensable molecule for regulating inflammation and immune response in multiple diseases,but the role of STING in the ALI pathogenesis is not well elucidated.In this study,we explored the molecular mechanisms of STING in regulating lipopolysaccharide(LPS)-induced lung injury.Mice were pretreated with a STING inhibitor C-176(15,30 mg/kg,i.p.)before LPS inhalation to induce ALI.We showed that LPS inhalation significantly increased STING expression in the lung tissues,whereas C-176 pretreatment dose-dependently suppressed the expression of STING,decreased the production of inflammatory cytokines including TNF-α,IL-6,IL-12,and IL-1β,and restrained the expression of chemokines and adhesion molecule vascular cell adhesion protein-1(VCAM-1)in the lung tissues.Consistently,in vitro experiments conducted in TNF-α-stimulated HMEC-1cells(common and classic vascular endothelial cells)revealed that human STING inhibitor H-151 or STING siRNA downregulated the expression levels of adhesion molecule and chemokines in HMEC-1cells,accompanied by decreased adhesive ability and chemotaxis of immunocytes upon TNF-αstimulation.We further revealed that STING inhibitor H-151 or STING knockdown significantly decreased the phosphorylation of transcription factor STAT1,which subsequently influenced its binding to chemokine CCL2 and adhesive molecule VCAM-1 gene promoter.Collectively,STING inhibitor can alleviate LPS-induced ALI in mice by preventing vascular endothelial cells–mediated immune cell chemotaxis and adhesion,suggesting that STING may be a promising therapeutic target for the treatment of ALI. | Bing Wu Meng-meng Xu Chen Fan Chun-lan Feng Qiu-kai Lu Hui-min Lu Cai-gui Xiang Fang Bai Hao-yu Wang Yan-wei Wu Wei Tang | 2022 | Acta Pharmacologica Sinica2022，43，8： | 3 |
| 15 | 泛素化修饰调控固有免疫信号通路的研究进展显示文摘宿主细胞依赖固有免疫系统识别入侵的病原微生物,经相关细胞信号转导通路,激活促炎症及抗感染的基因表达。泛素化修饰是细胞内广泛存在的蛋白质翻译后修饰机制,全方位调控宿主细胞防御病原微生物的动态过程:一方面,作为多功能的信号调节分子,在时空上精细调节免疫反应的进程,有效地清除入侵的病原体;另一方面,通过降解关键信号转导分子,限制过度免疫反应,避免造成宿主自体损伤。本文总结了泛素化修饰在Toll样受体信号通路(TLR)、RIG-I样受体信号通路(RLR)和STING介导的信号通路中的新功能,以及相关分子调控机制,并对前沿方向进行展望。 | 王强 崔晔 李森林 王琛 | 2015 | 生命的化学2015，35，2： | 3 |
| 16 | Autophagy receptor CCDC50 tunes the STING-mediated interferon response in viral infections and autoimmune diseases显示文摘DNA sensing and timely activation of interferon(IFN)-mediated innate immunity are crucial for the defense against DNA virus infections and the clearance of abnormal cells.However,overactivation of immune responses may lead to tissue damage and autoimmune diseases;therefore,these processes must be intricately regulated.STING is the key adaptor protein,which is activated by cyclic GMP-AMP,the second messenger derived from cGAS-mediated DNA sensing.Here,we report that CCDC50,a newly identified autophagy receptor,tunes STING-directed type I IFN signaling activity by delivering K63-polyubiquitinated STING to autolysosomes for degradation.Knockout of CCDC50 significantly increases herpes simplex virus 1(HSV-1)-or DNA ligand-induced production of type I IFN and proinflammatory cytokines.Ccdc50-deficient mice show increased production of IFN,decreased viral replication,reduced cell infiltration,and improved survival rates compared with their wild-type littermates when challenged with HSV-1.Remarkably,the expression of CCDC50 is downregulated in systemic lupus erythematosus(SLE),a chronic autoimmune disease.CCDC50 levels are negatively correlated with IFN signaling pathway activation and disease severity in human SLE patients.CCDC50 deficiency potentiates the cGAS-STING-mediated immune response triggered by SLE serum.Thus,our findings reveal the critical role of CCDC50 in the immune regulation of viral infections and autoimmune diseases and provide insights into the therapeutic implications of CCDC50 manipulation. | Panpan Hou Yuxin Lin Zibo Li Ruiqing Lu Yicheng Wang Tian Tian Penghui Jia Xi Zhang Liu Cao Zhongwei Zhou Chunmei Li Jieruo Gu Deyin Guo | 2021 | Cellular & Molecular Immunology2021，18，10： | 3 |
| 17 | cGAS——一种胞质DNA感应器的研究进展显示文摘机体天然免疫领域的最新研究发现了一系列具有感应胞内核酸作用的蛋白质,其中受到广泛关注且已经得到确认的是一种被称为cGAS的蛋白质。cGAS全称Cyclic guanosine monophosphate-adenosine monophosphate synthase,即环磷酸鸟苷-腺苷合成酶。大量的研究已经发现cGAS能感应入侵宿主细胞的病毒性或细菌性DNA,通过重要分子cGAMP、STING的相关作用,产生大量的干扰素以及其他种类的细胞因子,进而发挥重要的抗病毒作用。本文就cGAS-DNA感应通路以及cGAS与抗病毒免疫反应及自身免疫性疾病的研究进展进行综述,以期为其功能研究提供良好的理论基础。 | 原慧 陶佳丽 张亮 姜俊兵 | 2016 | 免疫学杂志2016，32，11： | 3 |
| 18 | Small-Molecule Targets in Tumor Immunotherapy显示文摘Cancer immunotherapy has been widely recognized as a powerful approach to fight cancers.To date,over 50 phase III trials in cancer immunotherapy are in progress.Among the many immunotherapy approaches,immune checkpoint therapy has attracted considerable attention.The reported clinical success of targeting the T cell immune checkpoint receptors PD-1 or CTLA4 by antibodies blockade in advanced stages of cancers has demonstrated the importance of immune modulation.But antibodies-based immunotherapy confronted with some disadvantages,such as immunogenicity,stability,membrane permeability,and production cost.Therefore,alternative approaches including small-molecule-regulated immune response are being introduced.In this review,we focused on some of the key intracellular pathways where small-molecule therapeutic is potential and attractive,which highlights the great potential of natural products in this field. | Hui-Fang Zhu Yan Li | 2018 | Natural Products and Bioprospecting2018，8，4： | 3 |
| 19 | cGAS-STING信号通路在心血管疾病中的作用显示文摘环鸟苷酸腺苷酸合成酶(cyclic GMP-AMP synthase,cGAS)作为一种DNA感受器通过识别胞质DNA产生环鸟苷酸-腺苷酸(cyclic GMP-AMP,cGAMP)并激活干扰素基因刺激因子(stimulator of interferon gene,STING)及一系列下游通路从而介导免疫及炎症反应。近年来研究发现,cGAS-STING所介导的信号通路在心肌梗死、心力衰竭、心肌炎等多种心血管疾病中被显著激活,提示其在心血管系统疾病的发病进程中扮演重要角色。为了更深入了解cGAS-STING信号通路在心血管疾病中的作用,该文就cGAS的生化特点、cGAS-STING介导的信号通路及其在心血管疾病中的作用等方面的研究进展进行综述。 | 向启中 张青海 郑昭芬 | 2022 | 中国细胞生物学学报2022，44，2： | 3 |
| 20 | 线粒体DNA与cGAS-STING固有免疫信号通路的研究前沿显示文摘线粒体是细胞中广泛存在的一种重要细胞器,除了管控细胞的能量制造和代谢外,线粒体还能参与细胞的抗感染、凋亡以及自噬等多种生物学过程。当外界环境或者细胞内部的有害刺激对线粒体造成应激反应时,线粒体会将包含其自身DNA(mitochondrial DNA,mtDNA)的线粒体基质释放到细胞质中。胞质内的mtDNA作为一种损伤相关分子模式,会激活不同的DNA模式识别受体,诱发机体的固有免疫反应。环化GMP-AMP合成酶(cGAS)是近些年来新发现的关键DNA受体,可通过催化形成第二信使cGAMP(2′3′-cGAMP)激活干扰素刺激基因(STING)依赖的信号通路。除了可抵抗病原微生感染,cGAS-STING信号通路在自身免疫、肿瘤和衰老等多种病理生理过程中均发挥重要作用。本综述主要讨论线粒体应激中释放的mtDNA如何激活cGAS-STING固有免疫信号通路以及与此相关的疾病,以期推动线粒体在固有免疫作用中的基础研究,并为以线粒体为靶点进行相关药物的开发提供新策略。 | 李永兴 崔淑方 孟卫 胡海洋 王琛 | 2021 | 四川大学学报(医学版)2021，52，3： | 3 |
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