[1]刘维,杨晨慧,乔梁,等.STING信号通路在非酒精性脂肪性肝病中作用的研究进展[J].国际内分泌代谢杂志,2023,43(04):325-329.[doi:10.3760/cma.j.cn121383-20220612-06027]
 Liu Wei,Yang Chenhui,Qiao Liang,et al.Update on the role of STING signaling pathway in the development of nonalcoholic fatty liver disease[J].International Journal of Endocrinology and Metabolism,2023,43(04):325-329.[doi:10.3760/cma.j.cn121383-20220612-06027]
点击复制

STING信号通路在非酒精性脂肪性肝病中作用的研究进展()
分享到:

《国际内分泌代谢杂志》[ISSN:1673-4157/CN:12-1383/R]

卷:
43
期数:
2023年04期
页码:
325-329
栏目:
综述
出版日期:
2023-07-20

文章信息/Info

Title:
Update on the role of STING signaling pathway in the development of nonalcoholic fatty liver disease
作者:
刘维杨晨慧乔梁谢绍锋曹琳
南京中医药大学附属中西医结合医院内分泌科,南京 210028
Author(s):
Liu Wei Yang Chenhui Qiao Liang Xie Shaofeng Cao Lin
Department of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China
关键词:
干扰素基因刺激因子 非酒精性脂肪性肝病 固有免疫
Keywords:
Stimulator of interferon genes Nonalcoholic fatty liver disease Innate immunity
DOI:
10.3760/cma.j.cn121383-20220612-06027
摘要:
非酒精性脂肪性肝病(NAFLD)已成为全球最常见的慢性肝病之一,目前尚无有效治疗措施。脂质代谢紊乱和肠道菌群失调诱导的固有免疫炎症在NAFLD进展中发挥重要作用。作为固有免疫的关键调控蛋白,干扰素基因刺激因子(STING)可通过识别胞浆DNA诱导Ⅰ型干扰素和其他细胞因子产生免疫应答,发挥抗病毒、抗肿瘤和免疫调节等作用。新近研究表明,STING介导的信号通路在巨噬细胞活化诱导的肝脏炎症及相关糖脂代谢紊乱中发挥关键作用,有望成为NAFLD治疗的新靶点。
Abstract:
Nonalcoholic fatty liver disease(NAFLD)has become the most common chronic liver disease worldwide. Until now, no therapeutic treatments have proven effective for NAFLD. Inflammation induced by dyslipidemia and gut dysbiosis plays an important role in NAFLD disease progression. As a key regulatory protein of innate immunity, stimulator of interferon genes(STING)can induce the production of interferons and other cytokines through recognizing cytoplasmic DNA to act for antiviral, immunomodulatory and antitumor functions. Recent studies have shown that the STING-mediated signaling pathway is crucial in the inflammation and relevant glycolipid metabolic disorders induced by the activation of hepatic macrophages, which is expected to become a new target for NAFLD treatment.

参考文献/References:

[1] Huang TD,Behary J,Zekry A.Non-alcoholic fatty liver disease:a review of epidemiology,risk factors,diagnosis and management[J].Intern Med J,2020,50(9):1038-1047.DOI:10.1111/imj.14709.
[2] Buzzetti E,Pinzani M,Tsochatzis EA.The multiple-hit pathogenesis of non-alcoholic fatty liver disease(NAFLD)[J].Metabolism,2016,65(8):1038-1048.DOI:10.1016/j.metabol.2015.12.012.
[3] Wang X,Rao H,Zhao J,et al.STING expression in monocyte-derived macrophages is associated with the progression of liver inflammation and fibrosis in patients with nonalcoholic fatty liver disease[J].Lab Invest,2020,100(4):542-552.DOI:10.1038/s41374-019-0342-6.
[4] Rada P,González-Rodríguez Á,García-Monzn C,et al.Understanding lipotoxicity in NAFLD pathogenesis:is CD36 a key driver?[J].Cell Death Dis,2020,11(9):802.DOI:10.1038/s41419-020-03003-w.
[5] Luo Z,Ji Y,Zhang D,et al.Microbial DNA enrichment promotes liver steatosis and fibrosis in the course of non-alcoholic steatohepatitis[J].Acta Physiol(Oxf),2022,235(3):e13827.DOI:10.1111/apha.13827.
[6] Sun L,Wu J,Du F,et al.Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type Ⅰ interferon pathway[J].Science,2013,339(6121):786-791.DOI:10.1126/science.1232458.
[7] Wu J,Sun L,Chen X,et al.Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA[J].Science,2013,339(6121):826-830.DOI:10.1126/science.1229963.
[8] Zhang C,Shang G,Gui X,et al.Structural basis of STING binding with and phosphorylation by TBK1[J].Nature,2019,567(7748):394-398.DOI:10.1038/s41586-019-1000-2.
[9] Balka KR,Louis C,Saunders TL,et al.TBK1 and IKKε act redundantly to mediate STING-induced NF-κB responses in myeloid cells[J].Cell Rep,2020,31(1):107492.DOI:10.1016/j.celrep.2020.03.056.
[10] Dunphy G,Flannery SM,Almine JF,et al.Non-canonical activation of the DNA sensing adaptor STING by ATM and IFI16 mediates NF-κB signaling after nuclear DNA damage[J].Mol Cell,2018,71(5):745-760.e5.DOI:10.1016/j.molcel.2018.07.034.
[11] Motwani M,Pesiridis S,Fitzgerald KA.DNA sensing by the cGAS-STING pathway in health and disease[J].Nat Rev Genet,2019,20(11):657-674.DOI:10.1038/s41576-019-0151-1.
[12] Yu Y,Liu Y,An W,et al.STING-mediated inflammation in Kupffer cells contributes to progression of nonalcoholic steatohepatitis[J].J Clin Invest,2019,129(2):546-555.DOI:10.1172/JCI121842.
[13] Luo Z,Ji Y,Gao H,et al.CRIg+ macrophages prevent gut microbial DNA-containing extracellular vesicle-induced tissue inflammation and insulin resistance[J].Gastroenterology,2021,160(3):863-874.DOI:10.1053/j.gastro.2020.10.042.
[14] 马林强.STING促进巨噬细胞介导的非酒精性脂肪肝病的进展[D].重庆:重庆医科大学,2019.
[15] Mao Y,Luo W,Zhang L,et al.STING-IRF3 triggers endothelial inflammation in response to free fatty acid-induced mitochondrial damage in diet-induced obesity[J].Arterioscler Thromb Vasc Biol,2017,37(5):920-929. DOI:10.1161/ATVBAHA.117.309017.
[16] Miyao M,Kotani H,Ishida T,et al.Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression[J].Lab Invest,2015,95(10):1130-1144.DOI:10.1038/labinvest.2015.95.
[17] Cho CS,Park HW,Ho A,et al.Lipotoxicity induces hepatic protein inclusions through TANK binding kinase 1-mediated p62/sequestosome 1 phosphorylation[J].Hepatology,2018,68(4):1331-1346.DOI:10.1002/hep.29742.
[18] Liu K,Qiu D,Liang X,et al.Lipotoxicity-induced STING1 activation stimulates MTORC1 and restricts hepatic lipophagy[J].Autophagy,2022,18(4):860-876.DOI:10.1080/15548627.2021.1961072.
[19] Akhmetova K,Balasov M,Chesnokov I.Drosophila STING protein has a role in lipid metabolism[J].Elife,2021,10:e67358.DOI:10.7554/eLife.67358.
[20] Qiao JT,Cui C,Qing L,et al.Activation of the STING-IRF3 pathway promotes hepatocyte inflammation,apoptosis and induces metabolic disorders in nonalcoholic fatty liver disease[J].Metabolism,2018,81:13-24.DOI:10.1016/j.metabol.2017.09.010.
[21] Cao L,Xu E,Zheng R,et al.Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages[J].Chin Med,2022,17(1):7.DOI:10.1186/s13020-021-00559-3.
[22] Li YN,Su Y.Remdesivir attenuates high fat diet(HFD)-induced NAFLD by regulating hepatocyte dyslipidemia and inflammation via the suppression of STING[J].Biochem Biophys Res Commun,2020,526(2):381-388.DOI:10.1016/j.bbrc.2020.03.034.
[23] Armandi A,Rosso C,Caviglia GP,et al.Insulin resistance across the spectrum of nonalcoholic fatty liver disease[J].Metabolites,2021,11(3):155.DOI:10.3390/metabo11030155.
[24] Hu H,Zhao R,He Q,et al.cGAS-STING mediates cytoplasmic mitochondrial-DNA-induced inflammatory signal transduction during accelerated senescence of pancreatic β-cells induced by metabolic stress[J].FASEB J,2022,36(5):e22266.DOI:10.1096/fj.202101988R.
[25] Hu HQ,Qiao JT,Liu FQ,et al.The STING-IRF3 pathway is involved in lipotoxic injury of pancreatic β cells in type 2 diabetes[J].Mol Cell Endocrinol,2020,518:110890.DOI:10.1016/j.mce.2020.110890.
[26] Iracheta-Vellve A,Petrasek J,Gyongyosi B,et al.Endoplasmic reticulum stress-induced hepatocellular death pathways mediate liver injury and fibrosis via stimulator of interferon genes[J].J Biol Chem,2016,291(52):26794-26805.DOI:10.1074/jbc.M116.736991.
[27] Thomsen MK,Skouboe MK,Boularan C,et al.The cGAS-STING pathway is a therapeutic target in a preclinical model of hepatocellular carcinoma[J].Oncogene,2020,39(8):1652-1664.DOI:10.1038/s41388-019-1108-8.
[28] Zhang Y,Zhai Q,Feng X,et al.Cancer cell-intrinsic STING is associated with CD8+T-cell infiltration and might serve as a potential immunotherapeutic target in hepatocellular carcinoma[J].Clin Transl Oncol,2021,23(7):1314-1324.DOI:10.1007/s12094-020-02519-z.
[29] 韦志行.cGAS-STING激动剂增强巨噬细胞对肝癌细胞吞噬作用的研究[D].济南:山东大学,2021.DOI:10.27272/d.cnki.gshdu.2021.003843.
[30] Dou Z,Ghosh K,Vizioli MG,et al.Cytoplasmic chromatin triggers inflammation in senescence and cancer[J].Nature,2017,550(7676):402-406.DOI:10.1038/nature24050.
[31] Garcia-Diaz A,Shin DS,Moreno BH,et al.Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression[J].Cell Rep,2017,19(6):1189-1201.DOI:10.1016/j.celrep.2017.04.031.
[32] Wu J,Dobbs N,Yang K,et al.Interferon-independent activities of mammalian STING mediate antiviral response and tumor immune evasion[J].Immunity,2020,53(1):115-126.e5.DOI:10.1016/j.immuni.2020.06.009.

相似文献/References:

[1]曹涵,曲伸.过氧化物酶体增殖物活化受体与非酒精性脂肪性肝病[J].国际内分泌代谢杂志,2014,(06):404.[doi:10.3760/cma.j.issn.1673-4157.2014.06.012]
 Cao Han,Qu Shen..Peroxisome proliferator-activated receptors and non-alcoholic fatty liver diseases[J].International Journal of Endocrinology and Metabolism,2014,(04):404.[doi:10.3760/cma.j.issn.1673-4157.2014.06.012]
[2]胡雅琴,包玉倩.维生素D对非酒精性脂肪性肝病的保护作用[J].国际内分泌代谢杂志,2014,(06):408.[doi:10.3760/cma.j.issn.1673-4157.2014.06.013]
 Hu Yaqin,Bao Yuqian..Protective effect of vitamin D on non-alcoholic fatty liver disease[J].International Journal of Endocrinology and Metabolism,2014,(04):408.[doi:10.3760/cma.j.issn.1673-4157.2014.06.013]
[3]聂秀玲,李明珍,孙丽荣.高尿酸血症与非酒精性脂肪性肝病[J].国际内分泌代谢杂志,2016,36(02):89.[doi:10.3760/cma.j.issn.1673-4157.2016.02.004]
 Nie Xiuling,Li Mingzhen,Sun Lirong..Hyperuricemia and non-alcoholic fatty liver[J].International Journal of Endocrinology and Metabolism,2016,36(04):89.[doi:10.3760/cma.j.issn.1673-4157.2016.02.004]
[4]张洁,邸阜生.运动防治非酒精性脂肪性肝病的机制[J].国际内分泌代谢杂志,2016,36(06):404.[doi:10.3760/cma.j.issn.1673-4157.2016.06.12]
 Zhang Jie,Di Fusheng..Mechanism of exercise on non-alcoholic fatty liver disease[J].International Journal of Endocrinology and Metabolism,2016,36(04):404.[doi:10.3760/cma.j.issn.1673-4157.2016.06.12]
[5]张雅楠,郗光霞,杨翠萍,等.自噬在非酒精性脂肪性肝病中的变化及作用[J].国际内分泌代谢杂志,2017,37(01):11.[doi:10.3760/cma.j.issn.1673-4157.2017.01.03]
 Zhang Yanan*,Xi Guangxia,Yang Cuiping,et al.The change and function of autophagy in nonalcoholic fatty liver disease[J].International Journal of Endocrinology and Metabolism,2017,37(04):11.[doi:10.3760/cma.j.issn.1673-4157.2017.01.03]
[6]李博,苏青.晚期糖基化终末产物及其受体与非酒精性脂肪性肝病的 关系[J].国际内分泌代谢杂志,2017,37(03):192.[doi:10.3760/cma.j.issn.1673-4157.2017.03.013]
 Li Bo,Su Qing..Relationship between advanced glycation end-products and its receptor in nonalcoholic fatty liver diseases[J].International Journal of Endocrinology and Metabolism,2017,37(04):192.[doi:10.3760/cma.j.issn.1673-4157.2017.03.013]
[7]狄红杰,刘超.饮食干预对非酒精性脂肪性肝病肠道菌群的影响[J].国际内分泌代谢杂志,2017,37(04):254.
 Di Hongjie,Liu Chao..Effects of diet interventions on gut microbiota of nonalcoholic fatty liver disease[J].International Journal of Endocrinology and Metabolism,2017,37(04):254.
[8]林楚曼 林伟浩 周蕊 杨力.GLP-1缓解非酒精性脂肪性肝病相关信号通路的研究进展[J].国际内分泌代谢杂志,2018,38(03):179.[doi:10.3760/cma.j.issn.1673-4157.2018.03.009]
 Lin Chuman*,Lin Weihao,Zhou Rui,et al.The research progresses on GLP-1 related signal pathways in alleviating non-alcoholic fatty liver disease[J].International Journal of Endocrinology and Metabolism,2018,38(04):179.[doi:10.3760/cma.j.issn.1673-4157.2018.03.009]
[9]李霞 雷涛.铁过载与代谢性疾病的关系[J].国际内分泌代谢杂志,2018,38(01):29.[doi:10.3760/cma.j.issn.1673-4157.2018.01.008]
 Li Xia*,Lei Tao..Relationship between iron overload and metabolic diseases[J].International Journal of Endocrinology and Metabolism,2018,38(04):29.[doi:10.3760/cma.j.issn.1673-4157.2018.01.008]
[10]曹白鸽 董艳.母体妊娠期高脂饮食所致的炎性反应状态对子代的影响[J].国际内分泌代谢杂志,2018,38(02):96.[doi:10.3760/cma.j.issn.1673-4157.2018.02.006]
 Cao Baige*,Dong Yan..Effects of inflammatory state on offspring induced by maternal high-fat diet during pregnancy[J].International Journal of Endocrinology and Metabolism,2018,38(04):96.[doi:10.3760/cma.j.issn.1673-4157.2018.02.006]

备注/Memo

备注/Memo:
基金项目:江苏省自然科学基金项目(BK20211388); 江苏省科技发展计划项目(ZT202207; MS2022029)
通信作者:曹琳,Email:guodongcl@163.com; 谢绍锋,Email:xiesf3562@sina.com
更新日期/Last Update: 2023-08-15