NLRP3炎症小体与相关炎症信号通路在肾缺血-再灌注损伤中的作用

袁强; 申开文; 张瑞波; 沈俊

doi:10.3969/j.issn.1674-7445.2021.02.007

NLRP3炎症小体与相关炎症信号通路在肾缺血-再灌注损伤中的作用

doi: 10.3969/j.issn.1674-7445.2021.02.007

550004 贵阳，贵州医科大学（袁强、申开文、张瑞波、沈俊）；贵州医科大学附属医院泌尿外科（袁强、申开文、张瑞波、沈俊）

基金项目:

贵州省科技计划项目（2018）5779-6

2020年国家自然科学基金培育项目（贵州医科大学附属医院） gyfynsfc（2020）-30

贵阳市政府-贵州医科大学联合基金 GY2017-16

详细信息

作者简介:
袁强，男，1993年生，硕士研究生，研究方向为肾移植相关缺血-再灌注损伤与保护，Email: 411057131@qq.com

通讯作者:
沈俊，男，1973年生，博士，副主任医师，研究方向为肾移植相关缺血-再灌注损伤与保护，Email: shenjun@gmc.edu.cn

中图分类号: R617
计量
- 文章访问数: 554
- HTML全文浏览量: 101
- PDF下载量: 57
- 被引次数: 0
出版历程
- 收稿日期: 2020-12-20
- 网络出版日期: 2021-03-19
- 刊出日期: 2021-03-15

Role of NLRP3 inflammasome and related inflammatory signaling pathways in renal ischemia-reperfusion injury

Guizhou Medical University, Guiyang 550004, China

More Information

Corresponding author: Shen Jun, Email: shenjun@gmc.edu.cn

摘要

摘要: 肾缺血-再灌注损伤（IRI）常见于肾移植术中，是引起急性肾衰竭的重要病理生理过程，严重影响受者预后。炎症反应在IRI的发病机制及病理过程中占据着重要地位。活化的NOD样受体蛋白3（NLRP3）炎症小体可通过介导多种促炎因子的成熟与释放，调节机体炎症反应及相关细胞功能。本文对肾IRI中的NLRP3炎症小体及其相关炎症信号通路的作用机制进行了总结，旨在为临床肾IRI的防治提供新思路。
- 缺血-再灌注损伤(IRI) /
- 肾移植 /
- NOD样受体蛋白3(NLRP3) /
- Toll样受体(TLR) /
- 模式识别受体(PRR) /
- 半胱氨酸天冬氨酸蛋白酶(Caspase)-1 /
- 线粒体DNA(mtDNA)
Abstract: Renal ischemia-reperfusion injury (IRI) commonly occurs in renal transplantation, which is an important pathophysiological process that causes acute renal failure and severely affects clinical prognosis of the recipients. Inflammatory response plays a critical role in the pathogenesis and pathological process of IRI. Activated NOD-like receptor protein 3(NLRP3) inflammasome can mediate the maturation and release of various pro-inflammatory cytokines, thereby regulating the inflammatory response and relevant cell functions. In this article, the mechanism underlying NLRP3 inflammasome and its related inflammatory signaling pathway in renal IRI were reviewed, aiming to provide novel ideas for clinical prevention and treatment of renal IRI.

HTML全文

下载: 全尺寸图片幻灯片

参考文献(45)

[1]	NIEUWENHUIJS-MOEKE GJ, PISCHKE SE, BERGER SP, et al. Ischemia and reperfusion injury in kidney transplantation: relevant mechanisms in injury and repair[J]. J Clin Med, 2020, 9(1): 253. DOI: 10.3390/jcm9010253.
[2]	ELTZSCHIG HK, ECKLE T. Ischemia and reperfusion--from mechanism to translation[J]. Nat Med, 2011, 17(11): 1391-1401. DOI: 10.1038/nm.2507.
[3]	JANSEN MP, EMAL D, TESKE GJ, et al. Release of extracellular DNA influences renal ischemia reperfusion injury by platelet activation and formation of neutrophil extracellular traps[J]. Kidney Int, 2017, 91(2): 352-364. DOI: 10.1016/j.kint.2016.08.006.
[4]	PARK JS, CHOI HI, BAE EH, et al. Small heterodimer partner attenuates hydrogen peroxide-induced expression of cyclooxygenase-2 and inducible nitric oxide synthase by suppression of activator protein-1 and nuclear factor-κB in renal proximal tubule epithelial cells[J]. Int J Mol Med, 2017, 39(3): 701-710. DOI: 10.3892/ijmm.2017.2883.
[5]	MULAY SR. Multifactorial functions of the inflammasome component NLRP3 in pathogenesis of chronic kidney diseases[J]. Kidney Int, 2019, 96(1): 58-66. DOI: 10.1016/j.kint.2019.01.014.
[6]	SHIM DW, LEE KH. Posttranslational regulation of the NLR family pyrin domain-containing 3 inflammasome[J]. Front Immunol, 2018, 9: 1054. DOI: 10.3389/fimmu.2018.01054.
[7]	BORTOLOTTI P, FAURE E, KIPNIS E. Inflammasomes in tissue damages and immune disorders after trauma[J]. Front Immunol, 2018, 9: 1900. DOI: 10.3389/fimmu.2018.01900.
[8]	WANG Z, ZHANG S, XIAO Y, et al. NLRP3 inflammasome and inflammatory diseases[J]. Oxid Med Cell Longev, 2020: 4063562. DOI: 10.1155/2020/4063562.
[9]	LAU A, CHUNG H, KOMADA T, et al. Renal immune surveillance and dipeptidase-1 contribute to contrast-induced acute kidney injury[J]. J Clin Invest, 2018, 128(7): 2894-2913. DOI: 10.1172/JCI96640.
[10]	LIU H, WU X, LUO J, et al. Adiponectin peptide alleviates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/GSK-3β[J]. Exp Neurol, 2020, 329: 113302. DOI: 10.1016/j.expneurol.2020.113302.
[11]	WANG Y, LIU X, SHI H, et al. NLRP3 inflammasome, an immune-inflammatory target in pathogenesis and treatment of cardiovascular diseases[J]. Clin Transl Med, 2020, 10(1): 91-106. DOI: 10.1002/ctm2.13.
[12]	ITO H, KIMURA H, KARASAWA T, et al. NLRP3 inflammasome activation in lung vascular endothelial cells contributes to intestinal ischemia/reperfusion-induced acute lung injury[J]. J Immunol, 2020, 205(5): 1393-1405. DOI: 10.4049/jimmunol.2000217.
[13]	GONG Y, CAO X, GONG L, et al. Sulforaphane alleviates retinal ganglion cell death and inflammation by suppressing NLRP3 inflammasome activation in a rat model of retinal ischemia/reperfusion injury[J]. Int J Immunopathol Pharmacol, 2019, 33. DOI: 10.1177/2058738419861777.
[14]	KELLEY N, JELTEMA D, DUAN Y, et al. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation[J]. Int J Mol Sci, 2019, 20(13): 3328. DOI: 10.3390/ijms20133328.
[15]	STUTZ A, KOLBE CC, STAHL R, et al. NLRP3 inflammasome assembly is regulated by phosphorylation of the pyrin domain[J]. J Exp Med, 2017, 214(6): 1725-1736. DOI: 10.1084/jem.20160933.
[16]	MEYERS AK, ZHU X. The NLRP3 inflammasome: metabolic regulation and contribution to inflammaging[J]. Cells, 2020, 9(8): 1808. DOI: 10.3390/cells9081808.
[17]	GAIDT MM, HORNUNG V. Alternative inflammasome activation enables IL-1β release from living cells[J]. Curr Opin Immunol, 2017, 44: 7-13. DOI: 10.1016/j.coi.2016.10.007.
[18]	KIM JK, JIN HS, SUH HW, et al. Negative regulators and their mechanisms in NLRP3 inflammasome activation and signaling[J]. Immunol Cell Biol, 2017, 95(7): 584-592. DOI: 10.1038/icb.2017.23.
[19]	SWANSON KV, DENG M, TING JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics[J]. Nat Rev Immunol, 2019, 19(8): 477-489. DOI: 10.1038/s41577-019-0165-0.
[20]	DI A, XIONG S, YE Z, et al. The TWIK2 potassium efflux channel in macrophages mediates NLRP3 inflammasome-induced inflammation[J]. Immunity, 2018, 49(1): 56-65. DOI: 10.1016/j.immuni.2018.04.032.
[21]	TANG T, LANG X, XU C, et al. CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation[J]. Nat Commun, 2017, 8(1): 202. DOI: 10.1038/s41467-017-00227-x.
[22]	MORETTI J, BLANDER JM. Increasing complexity of NLRP3 inflammasome regulation[J]. J Leukoc Biol, 2020, DOI: 10.1002/JLB.3MR0520-104RR[Epubahead of print].
[23]	ZHONG Z, LIANG S, SANCHEZ-LOPEZ E, et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation[J]. Nature, 2018, 560(7717): 198-203. DOI: 10.1038/s41586-018-0372-z.
[24]	CHEN KW, MONTELEONE M, BOUCHER D, et al. Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps[J]. Sci Immunol, 2018, 3(26): eaar6676. DOI: 10.1126/sciimmunol.aar6676.
[25]	ANDRADE-OLIVEIRA V, FORESTO-NETO O, WATANABE IKM, et al. Inflammation in renal diseases: new and old players[J]. Front Pharmacol, 2019, 10: 1192. DOI: 10.3389/fphar.2019.01192.
[26]	GU L, TAO Y, CHEN C, et al. Initiation of the inflammatory response after renal ischemia/reperfusion injury during renal transplantation[J]. Int Urol Nephrol, 2018, 50(11): 2027-2035. DOI: 10.1007/s11255-018-1918-6.
[27]	FUSCO R, SIRACUSA R, GENOVESE T, et al. Focus on the role of NLRP3 inflammasome in diseases[J]. Int J Mol Sci, 2020, 21(12): 4223. DOI: 10.3390/ijms21124223.
[28]	WEN Y, LIU YR, TANG TT, et al. mROS-TXNIP axis activates NLRP3 inflammasome to mediate renal injury during ischemic AKI[J]. Int J Biochem Cell Biol, 2018, 98: 43-53. DOI: 10.1016/j.biocel.2018.02.015.
[29]	IYER SS, PULSKENS WP, SADLER JJ, et al. Necrotic cells trigger a sterile inflammatory response through the NLRP3 inflammasome[J]. Proc Natl Acad Sci U S A, 2009, 106(48): 20388-20393. DOI: 10.1073/pnas.0908698106.
[30]	KIM HJ, LEE DW, RAVICHANDRAN K, et al. NLRP3 inflammasome knockout mice are protected against ischemic but not cisplatin-induced acute kidney injury[J]. J Pharmacol Exp Ther, 2013, 346(3): 465-472. DOI: 10.1124/jpet.113.205732.
[31]	KIM YG, KIM SM, KIM KP, et al. The role of inflammasome-dependent and inflammasome-independent NLRP3 in the kidney[J]. Cells, 2019, 8(11): 1389. DOI: 10.3390/cells8111389.
[32]	SCHNEIDER KS, GROß CJ, DREIER RF, et al. The inflammasome drives GSDMD-independent secondary pyroptosis and IL-1 release in the absence of Caspase-1 protease activity[J]. Cell Rep, 2017, 21(13): 3846-3859. DOI: 10.1016/j.celrep.2017.12.018.
[33]	SCHMID-BURGK JL, GAIDT MM, SCHMIDT T, et al. Caspase-4 mediates non-canonical activation of the NLRP3 inflammasome in human myeloid cells[J]. Eur J Immunol, 2015, 45(10): 2911-2917. DOI: 10.1002/eji.201545523.
[34]	SHIGEOKA AA, MUELLER JL, KAMBO A, et al. An inflammasome-independent role for epithelial-expressed NLRP3 in renal ischemia-reperfusion injury[J]. J Immunol, 2010, 185(10): 6277-6285. DOI: 10.4049/jimmunol.1002330.
[35]	KIM SM, KIM YG, KIM DJ, et al. Inflammasome-independent role of NLRP3 mediates mitochondrial regulation in renal injury[J]. Front Immunol, 2018, 9: 2563. DOI: 10.3389/fimmu.2018.02563.
[36]	LIAO Y, LIN X, LI J, et al. Nodakenin alleviates renal ischaemia-reperfusion injury via inhibiting reactive oxygen species-induced NLRP3 inflammasome activation[J]. Nephrology (Carlton), 2021, 26(1): 78-87. DOI: 10.1111/nep.13781.
[37]	YIN W, ZHOU QL, OUYANG SX, et al. Uric acid regulates NLRP3/IL-1β signaling pathway and further induces vascular endothelial cells injury in early CKD through ROS activation and K⁺ efflux[J]. BMC Nephrol, 2019, 20(1): 319. DOI: 10.1186/s12882-019-1506-8.
[38]	朱晔, 朱伟平, 李巍, 等. 表氧化二十碳三烯酸对小鼠肾缺血再灌注损伤NLRP3炎症小体表达及细胞焦亡的影响[J]. 中华医学杂志, 2020, 100(10): 779-784. DOI: 10.3760/cma.j.cn112137-20190803-01731. ZHU Y, ZHU WP, LI W, et al. Implications of EET in renal ischemia/reperfusion by regulating NLRP3 expression and pyroptosis[J]. Natl Med J China, 2020, 100(10): 779-784. DOI: 10.3760/cma.j.cn112137-20190803-01731.
[39]	NAZIR S, GADI I, AL-DABET MM, et al. Cytoprotective activated protein C averts NLRP3 inflammasome-induced ischemia-reperfusion injury via mTORC1 inhibition[J]. Blood, 2017, 130(24): 2664-2677. DOI: 10.1182/blood-2017-05-782102.
[40]	HUANG G, BAO J, SHAO X, et al. Inhibiting pannexin-1 alleviates sepsis-induced acute kidney injury via decreasing NLRP3 inflammasome activation and cell apoptosis[J]. Life Sci, 2020, 254: 117791. DOI: 10.1016/j.lfs.2020.117791.
[41]	HAN SJ, LOVASZI M, KIM M, et al. P2X4 receptor exacerbates ischemic AKI and induces renal proximal tubular NLRP3 inflammasome signaling[J]. FASEB J, 2020, 34(4): 5465-5482. DOI: 10.1096/fj.201903287R.
[42]	NEUDECKER V, HANEKLAUS M, JENSEN O, et al. Myeloid-derived miR-223 regulates intestinal inflammation via repression of the NLRP3 inflammasome[J]. J Exp Med, 2017, 214(6): 1737-1752. DOI: 10.1084/jem. 20160462.
[43]	WANG Y, HAN Z, FAN Y, et al. MicroRNA-9 inhibits NLRP3 inflammasome activation in human atherosclerosis inflammation cell models through the JAK1/STAT signaling pathway[J]. Cell Physiol Biochem, 2017, 41(4): 1555-1571. DOI: 10.1159/000470822.
[44]	CHEN S, SMITH BA, IYPE J, et al. MicroRNA-155-deficient dendritic cells cause less severe GVHD through reduced migration and defective inflammasome activation[J]. Blood, 2015, 126(1): 103-112. DOI: 10.1182/blood-2014-12-617258.
[45]	LECOEUR H, PRINA E, ROSAZZA T, et al. Targeting macrophage histone H3 modification as a leishmania strategy to dampen the NF-κB/NLRP3-mediated inflammatory response[J]. Cell Rep, 2020, 30(6): 1870-1882. DOI: 10.1016/j.celrep.2020.01.030.