Programmed Cell Death in Sepsis Associated Acute Kidney Injury

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2022 Jun 3

PMID 35655858

Authors

Zhifen Wu

Junhui Deng

Hongwen Zhou

Wei Tan

Lirong Lin

Jurong Yang

Affiliations

Soon will be listed here.

Abstract

Sepsis-associated acute kidney injury (SA-AKI) is common in patients with severe sepsis, and has a high incidence rate and high mortality rate in ICU patients. Most patients progress to AKI before drug treatment is initiated. Early studies suggest that the main mechanism of SA-AKI is that sepsis leads to vasodilation, hypotension and shock, resulting in insufficient renal blood perfusion, finally leading to renal tubular cell ischemia and necrosis. Research results in recent years have shown that programmed cell death such as apoptosis, necroptosis, pyroptosis and autophagy play important roles. In the early stage of sepsis-related AKI, autophagy bodies form and inhibit various types of programmed cell death. With the progress of disease, programmed cell death begins. Apoptosis promoter represents caspase-8-induced apoptosis and apoptosis effector represents caspase-3-induced apoptosis, however, caspase-11 and caspase-1 regulate gasdermin D-mediated pyroptosis. Caspase-8 and receptor interacting kinase 1 bodies mediate necroptosis. This review focuses on the pathophysiological mechanisms of various programmed cell death in sepsis-related AKI.

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References

Kufer T, Sansonetti P . Sensing of bacteria: NOD a lonely job. Curr Opin Microbiol. 2006; 10(1):62-9. DOI: 10.1016/j.mib.2006.11.003. View

Uchino S, Kellum J, Bellomo R, Doig G, Morimatsu H, Morgera S . Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005; 294(7):813-8. DOI: 10.1001/jama.294.7.813. View

Conos S, Chen K, De Nardo D, Hara H, Whitehead L, Nunez G . Active MLKL triggers the NLRP3 inflammasome in a cell-intrinsic manner. Proc Natl Acad Sci U S A. 2017; 114(6):E961-E969. PMC: 5307433. DOI: 10.1073/pnas.1613305114. View

Saitoh T, Fujita N, Jang M, Uematsu S, Yang B, Satoh T . Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature. 2008; 456(7219):264-8. DOI: 10.1038/nature07383. View

Upton J, Kaiser W, Mocarski E . Virus inhibition of RIP3-dependent necrosis. Cell Host Microbe. 2010; 7(4):302-313. PMC: 4279434. DOI: 10.1016/j.chom.2010.03.006. View

Duranton C, Rubera I, LHoste S, Cougnon M, Poujeol P, Barhanin J . KCNQ1 K+ channels are involved in lipopolysaccharide-induced apoptosis of distal kidney cells. Cell Physiol Biochem. 2010; 25(4-5):367-78. DOI: 10.1159/000303041. View

Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S, Lin X . New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature. 2018; 560(7717):198-203. PMC: 6329306. DOI: 10.1038/s41586-018-0372-z. View

Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson C . Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 2004; 6(12):1221-8. DOI: 10.1038/ncb1192. View

Cheng K, Xiong S, Ye Z, Hong Z, Di A, Tsang K . Caspase-11-mediated endothelial pyroptosis underlies endotoxemia-induced lung injury. J Clin Invest. 2017; 127(11):4124-4135. PMC: 5663346. DOI: 10.1172/JCI94495. View

10.

Panigrahi P, Parida S, Nanda N, Satpathy R, Pradhan L, Chandel D . A randomized synbiotic trial to prevent sepsis among infants in rural India. Nature. 2017; 548(7668):407-412. DOI: 10.1038/nature23480. View

11.

Zanoni I, Tan Y, Gioia M, Broggi A, Ruan J, Shi J . An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells. Science. 2016; 352(6290):1232-6. PMC: 5111085. DOI: 10.1126/science.aaf3036. View

12.

Fu Y, Wang D, Wang S, Zhang Q, Liu H, Yang S . Blockade of macrophage-associated programmed death 1 inhibits the pyroptosis signalling pathway in sepsis. Inflamm Res. 2021; 70(9):993-1004. DOI: 10.1007/s00011-021-01493-8. View

13.

Wu W, Wang J, Li Z, Wei B, Jin J, Gao L . 7-Hydroxycoumarin protects against cisplatin-induced acute kidney injury by inhibiting necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation. Phytomedicine. 2020; 69:153202. DOI: 10.1016/j.phymed.2020.153202. View

14.

Guo R, Wang Y, Minto A, Quigg R, Cunningham P . Acute renal failure in endotoxemia is dependent on caspase activation. J Am Soc Nephrol. 2004; 15(12):3093-102. DOI: 10.1097/01.ASN.0000145530.73247.F5. View

15.

Wu Y, Wang L, Meng L, Cao G, Zhao Y, Zhang Y . Biological effects of autophagy in mice with sepsis-induced acute kidney injury. Exp Ther Med. 2019; 17(1):316-322. PMC: 6307358. DOI: 10.3892/etm.2018.6899. View

16.

Yu L, Alva A, Su H, Dutt P, Freundt E, Welsh S . Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science. 2004; 304(5676):1500-2. DOI: 10.1126/science.1096645. View

17.

Bagshaw S, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G . Acute kidney injury in septic shock: clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med. 2008; 35(5):871-81. DOI: 10.1007/s00134-008-1367-2. View

18.

Klenzak J, Himmelfarb J . Sepsis and the kidney. Crit Care Clin. 2005; 21(2):211-22. DOI: 10.1016/j.ccc.2005.01.002. View

19.

Qiu T, Pei P, Yao X, Jiang L, Wei S, Wang Z . Taurine attenuates arsenic-induced pyroptosis and nonalcoholic steatohepatitis by inhibiting the autophagic-inflammasomal pathway. Cell Death Dis. 2018; 9(10):946. PMC: 6148242. DOI: 10.1038/s41419-018-1004-0. View

20.

Hultstrom M . Neurohormonal interactions on the renal oxygen delivery and consumption in haemorrhagic shock-induced acute kidney injury. Acta Physiol (Oxf). 2013; 209(1):11-25. DOI: 10.1111/apha.12147. View