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Knockout of Erbin promotes pyroptosis via regulating NLRP3/caspase-1/Gasdermin D pathway in sepsis-induced acute kidney injury

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Abstract

Background

This study aims to investigate the correlation between Erbin and sepsis, and the role of Erbin on the pyroptosis pathway in acute kidney injury caused by sepsis and NLRP3/caspase-1/Gasdermin D pathway.

Methods

In the study, lipopolysaccharide (LPS) treatment or cecal ligation and puncture (CLP) surgery on mice were used to stimulate the in vitro and in vivo sepsis-induced renal injury model. The male C57BL/6 of wild-type mice (WT) and Erbin-knockout mice (Erbin−/−, EKO) were randomly divided into four groups (WT + Sham, WT + CLP, EKO + Sham, EKO + CLP). Inflammatory cytokine, renal function, pyroptotic cell numbers and the levels of protein and mRNA expression of pyroptosis, including the NLRP3 (all P < 0.05), were analyzed and found increase in Erbin−/− mice with CLP and LPS-induced HK-2 cells.

Results

The inhibited of Erbin shows a renal damaged effect by promoting NLRP3 inflammasome-mediated pyroptosis in SI-AKI.

Conclusion

This study demonstrated a novel mechanism by which Erbin regulates NLRP3 inflammasome-mediated pyroptosis in SI-AKI.

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Data availability

All the authors have completed the data sharing statement. The original data inquiries can be directed to the corresponding authors.

References

  1. Prescott HC, Angus DC. Enhancing recovery from sepsis: a review. JAMA. 2018;319(1):62–75. https://doi.org/10.1001/jama.2017.17687.

    Article  PubMed  PubMed Central  Google Scholar 

  2. van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17(7):407–20. https://doi.org/10.1038/nri.2017.36.

    Article  CAS  PubMed  Google Scholar 

  3. Peerapornratana S, Manrique-Caballero CL, Gomez H, Kellum JA. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int. 2019;96(5):1083–99. https://doi.org/10.1016/j.kint.2019.05.026.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Skube SJ, Katz SA, Chipman JG, Tignanelli CJ. Acute kidney injury and sepsis. Surg Infect (Larchmt). 2018;19(2):216–24. https://doi.org/10.1089/sur.2017.261.

    Article  PubMed  Google Scholar 

  5. Deng J, Tan W, Luo Q, Lin L, Zheng L, Yang J. Long non-coding RNA MEG3 promotes renal tubular epithelial cell pyroptosis by regulating the miR-18a-3p/GSDMD pathway in lipopolysaccharide-induced acute kidney injury. Front Physiol. 2021;12:663216. https://doi.org/10.3389/fphys.2021.663216.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, et al. Inflammatory caspases are innate immune receptors for intracellular LPS. Nature. 2014;514(7521):187–92. https://doi.org/10.1038/nature13683.

    Article  CAS  PubMed  Google Scholar 

  7. Han Y, Xu X, Tang C, Gao P, Chen X, Xiong X, et al. Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis. Redox Biol. 2018;16:32–46. https://doi.org/10.1016/j.redox.2018.02.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Eldridge MJG, Sanchez-Garrido J, Hoben GF, Goddard PJ, Shenoy AR. The atypical ubiquitin E2 Conjugase UBE2L3 is an indirect caspase-1 target and controls IL-1β secretion by inflammasomes. Cell Rep. 2017;18(5):1285–97. https://doi.org/10.1016/j.celrep.2017.01.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Abu Khweek A, Amer AO. Pyroptotic and non-pyroptotic effector functions of caspase-11. Immunol Rev. 2020;297(1):39–52. https://doi.org/10.1111/imr.12910.

    Article  CAS  PubMed  Google Scholar 

  10. Strowig T, Henao-Mejia J, Elinav E, Flavell R. Inflammasomes in health and disease. Nature. 2012;481(7381):278–86. https://doi.org/10.1038/nature10759.

    Article  CAS  PubMed  Google Scholar 

  11. Zheng X, Chen W, Gong F, Chen Y, Chen E. The role and mechanism of pyroptosis and potential therapeutic targets in sepsis: a review. Front Immunol. 2021;12:711939. https://doi.org/10.3389/fimmu.2021.711939.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jang H, Stevens P, Gao T, Galperin E. The leucine-rich repeat signaling scaffolds Shoc2 and Erbin: cellular mechanism and role in disease. FEBS J. 2021;288(3):721–39. https://doi.org/10.1111/febs.15450.

    Article  CAS  PubMed  Google Scholar 

  13. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the global burden of disease study. Lancet. 2020;395(10219):200–11. https://doi.org/10.1016/S0140-6736(19)32989-7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Guven-Maiorov E, Keskin O, Gursoy A, VanWaes C, Chen Z, Tsai CJ, et al. The architecture of the TIR domain signalosome in the toll-like receptor-4 signaling pathway. Sci Rep. 2015;5:13128. https://doi.org/10.1038/srep13128.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Santoni MJ, Kashyap R, Camoin L, Borg JP. The scribble family in cancer: twentieth anniversary. Oncogene. 2020;39(47):7019–33. https://doi.org/10.1038/s41388-020-01478-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. McDonald C, Chen FF, Ollendorff V, Ogura Y, Marchetto S, Lecine P, et al. A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling. J Biol Chem. 2005;280(48):40301–9. https://doi.org/10.1074/jbc.M508538200.

    Article  CAS  PubMed  Google Scholar 

  17. Borg JP, Marchetto S, Le Bivic A, Ollendorff V, Jaulin-Bastard F, Saito H, et al. ERBIN: a basolateral PDZ protein that interacts with the mammalian ERBB2/HER2 receptor. Nat Cell Biol. 2000;2(7):407–14. https://doi.org/10.1038/35017038.

    Article  CAS  PubMed  Google Scholar 

  18. Wu XJ, Yang XM, Song XM, Xu Y, Li JG, Wang YL, et al. The role of Erbin in GTS-21 regulating inflammtory responses in MDP-stimulated macrophages. Shock. 2017;47(5):653–7. https://doi.org/10.1097/SHK.0000000000000785.

    Article  CAS  PubMed  Google Scholar 

  19. Yang JJ, Wu BB, Han F, Chen JH, Yang Y. Gene expression profiling of sepsis-associated acute kidney injury. Exp Ther Med. 2020;20(5):34. https://doi.org/10.3892/etm.2020.9161.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jiang J, Hu B, Chung CS, Chen Y, Zhang Y, Tindal EW, et al. SHP2 inhibitor PHPS1 ameliorates acute kidney injury by Erk1/2-STAT3 signaling in a combined murine hemorrhage followed by septic challenge model. Mol Med. 2020;26(1):89. https://doi.org/10.1186/s10020-020-00210-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Huang G, Bao J, Shao X, Zhou W, Wu B, Ni Z, et al. Inhibiting pannexin-1 alleviates sepsis-induced acute kidney injury via decreasing NLRP3 inflammasome activation and cell apoptosis. Life Sci. 2020;254:117791. https://doi.org/10.1016/j.lfs.2020.117791.

    Article  CAS  PubMed  Google Scholar 

  22. Chen X, He WT, Hu LC, Li JX, Fang Y, Wang X, et al. Pyroptosis is driven by non-selective gasdermin-D pore and its morphology is different from MLKL channel-mediated necroptosis. Cell Res. 2016;26(9):1007–20. https://doi.org/10.1038/cr.2016.100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Dan L, Shi M, Duan H, Han C, Guo N. Erbin, a negative regulator in diverse signal pathways. Curr Protein Pept Sci. 2010;11(8):759–64. https://doi.org/10.2174/138920310794557673.

    Article  PubMed  Google Scholar 

  24. Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. J Am Med Assoc. 2014;311(13):1308. https://doi.org/10.1001/jama.2014.2637.

    Article  CAS  Google Scholar 

  25. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10. https://doi.org/10.1001/jama.2016.0287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang QL, Xing W, Yu C, Gao M, Deng LT. ROCK1 regulates sepsis-induced acute kidney injury via TLR2-mediated endoplasmic reticulum stress/pyroptosis axis. Mol Immunol. 2021;138:99–109. https://doi.org/10.1016/j.molimm.2021.07.022.

    Article  CAS  PubMed  Google Scholar 

  27. Lin Q, Li S, Jiang N, Jin H, Shao X, Zhu X, et al. Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy. Autophagy. 2021;17(10):2975–90. https://doi.org/10.1080/15548627.2020.1848971.

    Article  CAS  PubMed  Google Scholar 

  28. Wallach D, Kang TB, Dillon CP, Green DR. Programmed necrosis in inflammation: toward identification of the effector molecules. Science. 2016;352(6281):aaf2154. https://doi.org/10.1126/science.aaf2154.

    Article  CAS  PubMed  Google Scholar 

  29. Jorgensen I, Rayamajhi M, Miao EA. Programmed cell death as a defence against infection. Nat Rev Immunol. 2017;17(3):151–64. https://doi.org/10.1038/nri.2016.147.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We wish to thank the timely help given by Dr. Junjie Xiao, Department of Physiology, Wuhan University, for his donation of HK-2 cells and guidance of this experiment.

Funding

The study was supported, in part, by a grant from the National Natural Science Foundation of China (87172144), Hubei Provincial Young Medical Talents (HBRC20200411).

Author information

Author notes

  1. Yuping Liu, Qing Fang, and Tingqian Ming contributed equally to this work.

Authors and Affiliations

  1. The Department of Research Centre of Anesthesiology and Critical Care Medicine Anesthesiology, Zhongnan Hospital of Wuhan University, Wuchang, Wuhan, 430071, Hubei Province, China

    Yuping Liu, Qing Fang, Jing Zuo, Guoqing Jing & Xuemin Song

  2. Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, China

    Yuping Liu

  3. Department of Anesthesiology, Nanfang Hospital of Southern Medical University, Guangzhou, China

    Tingqian Ming

Authors
  1. Yuping Liu
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  2. Qing Fang
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  4. Jing Zuo
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  5. Guoqing Jing
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  6. Xuemin Song
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Contributions

All the authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [YL], [QF] [TM] [JZ] [GJ] and [XS]. The first draft of the manuscript was written by [XS], and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Xuemin Song.

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Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

All the procedures performed in studies involving animals were in accordance with the ethical standards of the institutional or practice at which the studies were conducted (IRB approval number WQ20210298).

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Liu, Y., Fang, Q., Ming, T. et al. Knockout of Erbin promotes pyroptosis via regulating NLRP3/caspase-1/Gasdermin D pathway in sepsis-induced acute kidney injury. Clin Exp Nephrol 27, 781–790 (2023). https://doi.org/10.1007/s10157-023-02364-8

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  • DOI: https://doi.org/10.1007/s10157-023-02364-8

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