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Neutrophil Extracellular Traps Aggravate Contrast-Induced Acute Kidney Injury by Damaging Glomeruli and Peritubular Capillaries

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is considered to be the third leading cause of hospital-acquired kidney injury. Current studies mostly suggest that contrast agents mainly harm renal tubular epithelial cells, but we hypothesized that the development of CI-AKI should be the r...

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Autores principales: Wang, Heng, Gao, Tingting, Zhang, Ruijing, Hu, Jie, Gao, Siqi, Wang, Yuwen, Qi, Xiaotong, Zhou, Yun, Zheng, Guoping, Dong, Honglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693253/
https://www.ncbi.nlm.nih.gov/pubmed/38046404
http://dx.doi.org/10.2147/JIR.S433110
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author Wang, Heng
Gao, Tingting
Zhang, Ruijing
Hu, Jie
Gao, Siqi
Wang, Yuwen
Qi, Xiaotong
Zhou, Yun
Zheng, Guoping
Dong, Honglin
author_facet Wang, Heng
Gao, Tingting
Zhang, Ruijing
Hu, Jie
Gao, Siqi
Wang, Yuwen
Qi, Xiaotong
Zhou, Yun
Zheng, Guoping
Dong, Honglin
author_sort Wang, Heng
collection PubMed
description BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is considered to be the third leading cause of hospital-acquired kidney injury. Current studies mostly suggest that contrast agents mainly harm renal tubular epithelial cells, but we hypothesized that the development of CI-AKI should be the result of the interaction of renal vascular and tubular injury. METHODS: First we constructed a CI-AKI mouse model and verified the success of the model by pathological injury and serum creatinine level. Immunohistochemistry, protein quantification and qRT-PCR were used to detect the location and level of expression of neutrophil extracellular traps (NETs) in the kidney. Then, we blocked the in vivo accumulation of NETs using GSK484 and DNase I and detected the expression of NETs and the damage of glomerular and peritubular capillaries. RESULTS: We first identified the presence of NETs in CI-AKI mice, and NETs were mainly accumulated in glomeruli and peritubular capillaries. The expression of NETs was positively correlated with the severity of CI-AKI kidney. After inhibition of NETs release or promotion of NETs degradation by drugs, renal vascular endothelial cell injury was reduced and renal pathological changes and creatinine levels were reversed in CI-AKI mice. In addition, inhibition of NETs reduced apoptosis and pyroptosis of renal cells and attenuated inflammation in vivo. CONCLUSION: These findings suggest that NETs are involved in the development of CI-AKI by damaging glomerular and peritubular capillary endothelial cells. This study will provide a new strategy for clinical prevention and treatment of CI-AKI.
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spelling pubmed-106932532023-12-03 Neutrophil Extracellular Traps Aggravate Contrast-Induced Acute Kidney Injury by Damaging Glomeruli and Peritubular Capillaries Wang, Heng Gao, Tingting Zhang, Ruijing Hu, Jie Gao, Siqi Wang, Yuwen Qi, Xiaotong Zhou, Yun Zheng, Guoping Dong, Honglin J Inflamm Res Original Research BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is considered to be the third leading cause of hospital-acquired kidney injury. Current studies mostly suggest that contrast agents mainly harm renal tubular epithelial cells, but we hypothesized that the development of CI-AKI should be the result of the interaction of renal vascular and tubular injury. METHODS: First we constructed a CI-AKI mouse model and verified the success of the model by pathological injury and serum creatinine level. Immunohistochemistry, protein quantification and qRT-PCR were used to detect the location and level of expression of neutrophil extracellular traps (NETs) in the kidney. Then, we blocked the in vivo accumulation of NETs using GSK484 and DNase I and detected the expression of NETs and the damage of glomerular and peritubular capillaries. RESULTS: We first identified the presence of NETs in CI-AKI mice, and NETs were mainly accumulated in glomeruli and peritubular capillaries. The expression of NETs was positively correlated with the severity of CI-AKI kidney. After inhibition of NETs release or promotion of NETs degradation by drugs, renal vascular endothelial cell injury was reduced and renal pathological changes and creatinine levels were reversed in CI-AKI mice. In addition, inhibition of NETs reduced apoptosis and pyroptosis of renal cells and attenuated inflammation in vivo. CONCLUSION: These findings suggest that NETs are involved in the development of CI-AKI by damaging glomerular and peritubular capillary endothelial cells. This study will provide a new strategy for clinical prevention and treatment of CI-AKI. Dove 2023-11-28 /pmc/articles/PMC10693253/ /pubmed/38046404 http://dx.doi.org/10.2147/JIR.S433110 Text en © 2023 Wang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Wang, Heng
Gao, Tingting
Zhang, Ruijing
Hu, Jie
Gao, Siqi
Wang, Yuwen
Qi, Xiaotong
Zhou, Yun
Zheng, Guoping
Dong, Honglin
Neutrophil Extracellular Traps Aggravate Contrast-Induced Acute Kidney Injury by Damaging Glomeruli and Peritubular Capillaries
title Neutrophil Extracellular Traps Aggravate Contrast-Induced Acute Kidney Injury by Damaging Glomeruli and Peritubular Capillaries
title_full Neutrophil Extracellular Traps Aggravate Contrast-Induced Acute Kidney Injury by Damaging Glomeruli and Peritubular Capillaries
title_fullStr Neutrophil Extracellular Traps Aggravate Contrast-Induced Acute Kidney Injury by Damaging Glomeruli and Peritubular Capillaries
title_full_unstemmed Neutrophil Extracellular Traps Aggravate Contrast-Induced Acute Kidney Injury by Damaging Glomeruli and Peritubular Capillaries
title_short Neutrophil Extracellular Traps Aggravate Contrast-Induced Acute Kidney Injury by Damaging Glomeruli and Peritubular Capillaries
title_sort neutrophil extracellular traps aggravate contrast-induced acute kidney injury by damaging glomeruli and peritubular capillaries
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693253/
https://www.ncbi.nlm.nih.gov/pubmed/38046404
http://dx.doi.org/10.2147/JIR.S433110
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