Knocking Down ETS Proto-oncogene 1 (ETS1) Alleviates the Pyroptosis of Renal Tubular Epithelial Cells in Patients with Acute Kidney Injury by Regulating the NLR Family Pyrin Domain Containing 3 (NLRP3) Transcription

Overview

Journal Bioengineered

Date 2022 May 25

PMID 35611792

Authors

Chenxia Juan

Ye Zhu

Yan Chen

Yan Mao

Yan Zhou

Weiwei Zhu

Xufang Wang

Qian Wang

Affiliations

Soon will be listed here.

Abstract

Acute kidney injury (AKI) has a high mortality rate, but its pathogenesis remains unclear Lipopolysaccharide (LPS)-mediated renal tubular epithelial pyroptosis is involved in the pathogenesis of AKI. NLR family of pyrin domains containing 3 (NLRP3) plays an important role in pyroptosis. To further understand the transcriptional regulation mechanism of NLRP3, the peripheral blood of patients with AKI was analyzed in this study, showing that the levels of NLRP3 and cell pyroptosis in patients with AKI were significantly higher than those in normal controls. Furthermore, elevated levels of NLRP3 and cell pyroptosis were found in renal tubular epithelial cells after LPS treatment. Transcription factor ETS Proto-Oncogene 1 (ETS1) could bind to the upstream promoter transcription site of NLRP3 to transactivate NLRP3 in renal tubular epithelial cells. The cell pyroptosis level also decreased by knocking down ETS1. It is concluded that knocking down of ETS1 may reduce the renal tubular epithelial pyroptosis by regulating the transcription of NLRP3, thus relieving AKI. ETS1 is expected to be a molecular target for the treatment of AKI.

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References

Chou X, Ding F, Zhang X, Ding X, Gao H, Wu Q . Sirtuin-1 ameliorates cadmium-induced endoplasmic reticulum stress and pyroptosis through XBP-1s deacetylation in human renal tubular epithelial cells. Arch Toxicol. 2019; 93(4):965-986. DOI: 10.1007/s00204-019-02415-8. View

He L, Wei Q, Liu J, Yi M, Liu Y, Liu H . AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms. Kidney Int. 2017; 92(5):1071-1083. PMC: 5683166. DOI: 10.1016/j.kint.2017.06.030. View

McCoy I, Chertow G . AKI-A Relevant Safety End Point?. Am J Kidney Dis. 2020; 75(4):508-512. PMC: 7092818. DOI: 10.1053/j.ajkd.2019.11.010. View

Groslambert M, Py B . [Regulation of the NLRP3 inflammasome]. Med Sci (Paris). 2018; 34(1):47-53. DOI: 10.1051/medsci/20183401013. View

Nakazawa D, Kumar S, Marschner J, Desai J, Holderied A, Rath L . Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI. J Am Soc Nephrol. 2017; 28(6):1753-1768. PMC: 5461800. DOI: 10.1681/ASN.2016080925. View

Liang K, Sileanu F, Clermont G, Murugan R, Pike F, Palevsky P . Modality of RRT and Recovery of Kidney Function after AKI in Patients Surviving to Hospital Discharge. Clin J Am Soc Nephrol. 2015; 11(1):30-8. PMC: 4702218. DOI: 10.2215/CJN.01290215. View

Goszczynski D, Halstead M, Islas-Trejo A, Zhou H, Ross P . Transcription initiation mapping in 31 bovine tissues reveals complex promoter activity, pervasive transcription, and tissue-specific promoter usage. Genome Res. 2021; 31(4):732-744. PMC: 8015843. DOI: 10.1101/gr.267336.120. View

Han S, Williams R, Kim M, Heller D, DAgati V, Schmidt-Supprian M . Renal proximal tubular NEMO plays a critical role in ischemic acute kidney injury. JCI Insight. 2020; 5(19). PMC: 7566738. DOI: 10.1172/jci.insight.139246. View

Lu L, Zhong Z, Gu J, Nan K, Zhu M, Miao C . ets1 associates with KMT5A to participate in high glucose-mediated EndMT via upregulation of PFN2 expression in diabetic nephropathy. Mol Med. 2021; 27(1):74. PMC: 8266168. DOI: 10.1186/s10020-021-00339-7. View

10.

Feng W, Guan Z, Xing D, Li X, Ying W, Remedies C . Avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) plays a role in renal microvascular pathophysiology in the Dahl salt-sensitive rat. Kidney Int. 2020; 97(3):528-537. PMC: 7039742. DOI: 10.1016/j.kint.2019.09.025. View

11.

Wang X, Shu J, Jiang C, Zhuang L, Yang W, Zhang H . Mechanisms and roles by which IRF-3 mediates the regulation of ORMDL3 transcription in respiratory syncytial virus infection. Int J Biochem Cell Biol. 2017; 87:8-17. DOI: 10.1016/j.biocel.2017.03.007. View

12.

Chan A, Schroder K . Inflammasome signaling and regulation of interleukin-1 family cytokines. J Exp Med. 2019; 217(1). PMC: 7037238. DOI: 10.1084/jem.20190314. View

13.

Van Opdenbosch N, Lamkanfi M . Caspases in Cell Death, Inflammation, and Disease. Immunity. 2019; 50(6):1352-1364. PMC: 6611727. DOI: 10.1016/j.immuni.2019.05.020. View

14.

Zhou G, Wong C, Su R, Crable S, Anderson K, Gallagher P . Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element. Blood. 2004; 103(11):4302-9. DOI: 10.1182/blood-2003-01-0107. View

15.

Oettgen P . Regulation of vascular inflammation and remodeling by ETS factors. Circ Res. 2006; 99(11):1159-66. DOI: 10.1161/01.RES.0000251056.85990.db. View

16.

Lin Q, Li S, Jiang N, Jin H, Shao X, Zhu X . Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy. Autophagy. 2020; 17(10):2975-2990. PMC: 8525960. DOI: 10.1080/15548627.2020.1848971. View

17.

Ni J, Jiang L, Shen G, Xia Z, Zhang L, Xu J . Hydrogen sulfide reduces pyroptosis and alleviates ischemia-reperfusion-induced acute kidney injury by inhibiting NLRP3 inflammasome. Life Sci. 2021; 284:119466. DOI: 10.1016/j.lfs.2021.119466. View

18.

OHara S, Splinter P, Trussoni C, Lorenzo Pisarello M, Loarca L, Splinter N . ETS Proto-oncogene 1 Transcriptionally Up-regulates the Cholangiocyte Senescence-associated Protein Cyclin-dependent Kinase Inhibitor 2A. J Biol Chem. 2017; 292(12):4833-4846. PMC: 5377799. DOI: 10.1074/jbc.M117.777409. View

19.

OHara S, Splinter P, Trussoni C, Guicciardi M, Splinter N, Al Suraih M . The transcription factor ETS1 promotes apoptosis resistance of senescent cholangiocytes by epigenetically up-regulating the apoptosis suppressor BCL2L1. J Biol Chem. 2019; 294(49):18698-18713. PMC: 6901313. DOI: 10.1074/jbc.RA119.010176. View

20.

Cao H, Liang J, Liu J, He Y, Ke Y, Sun Y . Novel Effects of Combination Therapy Through Inhibition of Caspase-1/Gasdermin D Induced-Pyroptosis in Lupus Nephritis. Front Immunol. 2021; 12:720877. PMC: 8639704. DOI: 10.3389/fimmu.2021.720877. View