Research progress on the role of STING signal pathway in ischemia-reperfusion injury

Hu Haoran; Xu Jian; Zhou Haoming

doi:10.3969/j.issn.1674-7445.2022.05.007

Volume 13 Issue 5

Sep. 2022

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Hu Haoran, Xu Jian, Zhou Haoming. Research progress on the role of STING signal pathway in ischemia-reperfusion injury[J]. ORGAN TRANSPLANTATION, 2022, 13(5): 591-596. doi: 10.3969/j.issn.1674-7445.2022.05.007

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Research progress on the role of STING signal pathway in ischemia-reperfusion injury

doi: 10.3969/j.issn.1674-7445.2022.05.007

Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

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Corresponding author: Zhou Haoming, Email: hmzhou@njmu.edu.cn
Received Date: 2022-04-24
Available Online: 2022-09-14
Publish Date: 2022-09-15

Abstract

Abstract

Ischemia-reperfusion injury (IRI) is a pathophysiological process, which widely exists in organ transplantation and surgery. IRI is mainly manifested with hypoxia injury of organs or tissues during the ischemia period, which could be further aggravated after reperfusion. Ischemia-reperfusion induces tissue cell injury, releases damage-associated molecular pattern and further activates multiple immune cells via pattern recognition receptor, leading to aseptic inflammation and aggravating tissue injury. Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), as a critical member of pattern recognition receptor, could activate the stimulator of interferon genes (STING) signal pathway and play an important regulatory role in innate immune response. At present, increasing evidences have shown that cGAS-STING signal pathway plays a significant role in organ IRI. In this article, STING signaling pathway, its role and mechanism in IRI of different organs were reviewed, aiming to provide novel ideas for clinical interventions.
- Ischemia-reperfusion injury,
- Stimulator of interferon genes,
- Inflammation,
- Innate immunity,
- Macrophage,
- Pattern recognition receptor,
- Autophagy,
- Cell death

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References(47)

References

[1]	KUMAR V. A STING to inflammation and autoimmunity[J]. J Leukoc Biol, 2019, 106(1): 171-185. DOI: 10.1002/JLB.4MIR1018-397RR.
[2]	KWON J, BAKHOUM SF. The cytosolic DNA-sensing cGAS-STING pathway in cancer[J]. Cancer Discov, 2020, 10(1): 26-39. DOI: 10.1158/2159-8290.CD-19-0761.
[3]	DAR WA, SULLIVAN E, BYNON JS, et al. Ischaemia reperfusion injury in liver transplantation: cellular and molecular mechanisms[J]. Liver Int, 2019, 39(5): 788-801. DOI: 10.1111/liv.14091.
[4]	ZHANG S, DU X, ZHANG K, et al. Effects of sevoflurane on apoptosis of myocardial cells in IRI rats[J]. Biomed Res Int, 2021: 3347949. DOI: 10.1155/2021/3347949.
[5]	PEFANIS A, IERINO FL, MURPHY JM, et al. Regulated necrosis in kidney ischemia-reperfusion injury[J]. Kidney Int, 2019, 96(2): 291-301. DOI: 10.1016/j.kint.2019.02.009.
[6]	龙嘉琪, 李跃兵. 肺缺血再灌注损伤炎症与自噬相关性的研究进展[J]. 实用医学杂志, 2022, 38(12): 1558-1562. DOI: 10.3969/j.issn.1006-5725.2022.12.021. LONG JQ, LI YB. Research progress on the correlation between inflammation and autophagy in lung ischemia reperfusion injury[J]. J Pract Med, 2022, 38(12): 1558-1562. DOI: 10.3969/j.issn.1006-5725.2022.12.021.
[7]	YAN HF, TUO QZ, YIN QZ, et al. The pathological role of ferroptosis in ischemia/reperfusion-related injury[J]. Zool Res, 2020, 41(3): 220-230. DOI: 10.24272/j.issn.2095-8137.2020.042.
[8]	WANG H, XI Z, DENG L, et al. Macrophage polarization and liver ischemia-reperfusion injury[J]. Int J Med Sci, 2021, 18(5): 1104-1113. DOI: 10.7150/ijms.52691.
[9]	NARDO B, CARACENI P, PASINI P, et al. Increased generation of reactive oxygen species in isolated rat fatty liver during postischemic reoxygenation[J]. Transplantation, 2001, 71(12): 1816-1820. DOI: 10.1097/00007890-200106270-00018.
[10]	胡莎莎, 刘钰, 王朝阳, 等. HMGB1/Caspase-1/GSDMD信号轴介导肝细胞焦亡在肝脏缺血-再灌注损伤中的作用[J]. 器官移植, 2022, 13(1): 88-97. DOI: 10.3969/j.issn.1674-7445.2022.01.014. HU SS, LIU Y, WANG ZY, et al. Effect of HMGB1/Caspase-1/GSDMD signaling axis-mediated hepatocyte pyroptosis on liver ischemia-reperfusion injury[J]. Organ Transplant, 2022, 13(1): 88-97. DOI: 10.3969/j.issn.1674-7445.2022.01.014.
[11]	SILVIS MJM, KAFFKA GENAAMD DENGLER SE, ODILLE CA, et al. Damage-associated molecular patterns in myocardial infarction and heart transplantation: the road to translational success[J]. Front Immunol, 2020, 11: 599511. DOI: 10.3389/fimmu.2020.599511.
[12]	LU L, ZHOU H, NI M, et al. Innate immune regulations and liver ischemia-reperfusion injury[J]. Transplantation, 2016, 100(12): 2601-2610. DOI: 10.1097/TP.0000000000001411.
[13]	DEWOLF SE, KASIMSETTY SG, HAWKES AA, et al. DAMPs released from injured renal tubular epithelial cells activate innate immune signals in healthy renal tubular epithelial cells[J]. Transplantation, 2021, 106(8): 1589-1599. DOI: 10.1097/TP.0000000000004038.
[14]	HUANG H, TOHME S, AL-KHAFAJI AB, et al. Damage-associated molecular pattern-activated neutrophil extracellular trap exacerbates sterile inflammatory liver injury[J]. Hepatology, 2015, 62(2): 600-614. DOI: 10.1002/hep.27841.
[15]	ISHIKAWA H, BARBER GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling[J]. Nature, 2008, 455(7213): 674-678. DOI: 10.1038/nature07317.
[16]	WU JJ, ZHAO L, HU HG, et al. Agonists and inhibitors of the STING pathway: potential agents for immunotherapy[J]. Med Res Rev, 2020, 40(3): 1117-1141. DOI: 10.1002/med.21649.
[17]	HOPFNER KP, HORNUNG V. Molecular mechanisms and cellular functions of cGAS-STING signalling[J]. Nat Rev Mol Cell Biol, 2020, 21(9): 501-521. DOI: 10.1038/s41580-020-0244-x.
[18]	FANG R, JIANG Q, GUAN Y, et al. Golgi apparatus-synthesized sulfated glycosaminoglycans mediate polymerization and activation of the cGAMP sensor STING[J]. Immunity, 2021, 54(5): 962-975. DOI: 10.1016/j.immuni.2021.03.011.
[19]	CHEN Q, SUN L, CHEN ZJ. Regulation and function of the cGAS-STING pathway of cytosolic DNA sensing[J]. Nat Immunol, 2016, 17(10): 1142-1149. DOI: 10.1038/ni.3558.
[20]	FANG R, WANG C, JIANG Q, et al. NEMO-IKKβ are essential for IRF3 and NF-κB activation in the cGAS-STING pathway[J]. J Immunol, 2017, 199(9): 3222-3233. DOI: 10.4049/jimmunol.1700699.
[21]	WU XY, CHEN YJ, LIU CA, et al. STING induces liver ischemia-reperfusion injury by promoting calcium-dependent caspase 1-GSDMD processing in macrophages[J]. Oxid Med Cell Longev, 2022: 8123157. DOI: 10.1155/2022/8123157.
[22]	SHEN A, ZHENG D, LUO Y, et al. MicroRNA-24-3p alleviates hepatic ischemia and reperfusion injury in mice through the repression of STING signaling[J]. Biochem Biophys Res Commun, 2020, 522(1): 47-52. DOI: 10.1016/j.bbrc.2019.10.182.
[23]	LEI Z, DENG M, YI Z, et al. cGAS-mediated autophagy protects the liver from ischemia-reperfusion injury independently of STING[J]. Am J Physiol Gastrointest Liver Physiol, 2018, 314(6): G655-G667. DOI: 10.1152/ajpgi.00326.2017.
[24]	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.
[25]	LUO X, LI H, MA L, et al. Expression of STING is increased in liver tissues from patients with NAFLD and promotes macrophage-mediated hepatic inflammation and fibrosis in mice[J]. Gastroenterology, 2018, 155(6): 1971-1984. DOI: 10.1053/j.gastro.2018.09.010.
[26]	ZHONG W, RAO Z, RAO J, et al. Aging aggravated liver ischemia and reperfusion injury by promoting STING-mediated NLRP3 activation in macrophages[J]. Aging Cell, 2020, 19(8): e13186. DOI: 10.1111/acel.13186.
[27]	张熙, 黄兵, 王贵鹏. NLRP3炎症小体与心肌缺血再灌注损伤的研究进展[J]. 协和医学杂志, 2022, 13(2): 296-301. DOI: 10.12290/xhyxzz.2021-0619. ZHANG X, HUANG B, WANG GP. Progress of NLRP3 inflammasome and myocardial ischemia reperfusion injury[J]. Med J PUMCH, 2022, 13(2): 296-301. DOI: 10.12290/xhyxzz.2021-0619.
[28]	CAO DJ, SCHIATTARELLA GG, VILLALOBOS E, et al. Cytosolic DNA sensing promotes macrophage transformation and governs myocardial ischemic injury[J]. Circulation, 2018, 137(24): 2613-2634. DOI: 10.1161/CIRCULATIONAHA.117.031046.
[29]	KING KR, AGUIRRE AD, YE YX, et al. IRF3 and type I interferons fuel a fatal response to myocardial infarction[J]. Nat Med, 2017, 23(12): 1481-1487. DOI: 10.1038/nm.4428.
[30]	TER HORST EN, KRIJNEN PAJ, HAKIMZADEH N, et al. Elevated monocyte-specific type I interferon signalling correlates positively with cardiac healing in myocardial infarct patients but interferon alpha application deteriorates myocardial healing in rats[J]. Basic Res Cardiol, 2018, 114(1): 1. DOI: 10.1007/s00395-018-0709-7.
[31]	HU S, GAO Y, GAO R, et al. The selective STING inhibitor H-151 preserves myocardial function and ameliorates cardiac fibrosis in murine myocardial infarction[J]. Int Immunopharmacol, 2022, 107: 108658. DOI: 10.1016/j.intimp.2022.108658.
[32]	YU S, FU J, WANG J, et al. The influence of mitochondrial-DNA-driven inflammation pathways on macrophage polarization: a new perspective for targeted immunometabolic therapy in cerebral ischemia-reperfusion injury[J]. Int J Mol Sci, 2021, 23(1): 135. DOI: 10.3390/ijms23010135.
[33]	LIAO Y, CHENG J, KONG X, et al. HDAC3 inhibition ameliorates ischemia/reperfusion-induced brain injury by regulating the microglial cGAS-STING pathway[J]. Theranostics, 2020, 10(21): 9644-9662. DOI: 10.7150/thno.47651.
[34]	JIANG GL, YANG XL, ZHOU HJ, et al. cGAS knockdown promotes microglial M2 polarization to alleviate neuroinflammation by inhibiting cGAS-STING signaling pathway in cerebral ischemic stroke[J]. Brain Res Bull, 2021, 171: 183-195. DOI: 10.1016/j.brainresbull.2021.03.010.
[35]	GAMDZYK M, DOYCHEVA DM, ARAUJO C, et al. cGAS/STING pathway activation contributes to delayed neurodegeneration in neonatal hypoxia-ischemia rat model: possible involvement of LINE-1[J]. Mol Neurobiol, 2020, 57(6): 2600-2619. DOI: 10.1007/s12035-020-01904-7.
[36]	LI L, QIN JJ, GUO S, et al. Attenuation of cerebral ischemic injury in interferon regulatory factor 3-deficient rat[J]. J Neurochem, 2016, 136(4): 871-883. DOI: 10.1111/jnc.13448.
[37]	LIN F, YAO X, KONG C, et al. 25-Hydroxycholesterol protecting from cerebral ischemia-reperfusion injury through the inhibition of STING activity[J]. Aging (Albany NY), 2021, 13(16): 20149-20163. DOI: 10.18632/aging.203337.
[38]	MALLICK IH, YANG W, WINSLET MC, et al. Ischemia-reperfusion injury of the intestine and protective strategies against injury[J]. Dig Dis Sci, 2004, 49(9): 1359-1377. DOI: 10.1023/b:ddas.0000042232.98927.91.
[39]	TASSOPOULOS A, CHALKIAS A, PAPALOIS A, et al. The effect of antioxidant supplementation on bacterial translocation after intestinal ischemia and reperfusion[J]. Redox Rep, 2017, 22(1): 1-9. DOI: 10.1080/13510002.2016.1229893.
[40]	ZHANG X, WU J, LIU Q, et al. mtDNA-STING pathway promotes necroptosis-dependent enterocyte injury in intestinal ischemia reperfusion[J]. Cell Death Dis, 2020, 11(12): 1050. DOI: 10.1038/s41419-020-03239-6.
[41]	HU Q, REN H, LI G, et al. STING-mediated intestinal barrier dysfunction contributes to lethal sepsis[J]. EBioMedicine, 2019, 41: 497-508. DOI: 10.1016/j.ebiom.2019.02.055.
[42]	WU J, LIU Q, ZHANG X, et al. STING-dependent induction of lipid peroxidation mediates intestinal ischemia-reperfusion injury[J]. Free Radic Biol Med, 2021, 163: 135-140. DOI: 10.1016/j.freeradbiomed.2020.12.010.
[43]	CANESSO MCC, LEMOS L, NEVES TC, et al. The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation[J]. Mucosal Immunol, 2018, 11(3): 820-834. DOI: 10.1038/mi.2017.88.
[44]	BAI J, LIU F. cGAS‒STING signaling and function in metabolism and kidney diseases[J]. J Mol Cell Biol, 2021, 13(10): 728-738. DOI: 10.1093/jmcb/mjab066.
[45]	MAEKAWA H, INOUE T, OUCHI H, et al. Mitochondrial damage causes inflammation via CGAS-sting signaling in acute kidney injury[J]. Cell Rep, 2019, 29(5): 1261-1273. DOI: 10.1016/j.celrep.2019.09.050.
[46]	CHUNG KW, DHILLON P, HUANG S, et al. Mitochondrial damage and activation of the sting pathway lead to renal inflammation and fibrosis[J]. Cell Metab, 2019, 30(4): 784-799. DOI: 10.1016/j.cmet.2019.08.003.
[47]	FREITAS MC, UCHIDA Y, LASSMAN C, et al. Type I interferon pathway mediates renal ischemia/reperfusion injury[J]. Transplantation, 2011, 92(2): 131-138. DOI: 10.1097/TP.0b013e318220586e.

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Research progress on the role of STING signal pathway in ischemia-reperfusion injury

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