Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney

Brain death (BD) induces an organ-level inflammatory response. However, the underlying mechanisms have not been fully elucidated. Here, we investigated the role of caspase-1-mediated pyroptosis in BD-induced kidney injury in rats. A BD model was established in Sprague-Dawley rats. The rats were intr...

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Autores principales:	Weifeng Liu, Dongjing Yang, Jihua Shi, Peihao Wen, Jiakai Zhang, Zhihui Wang, Bowen Hu, Xiaoyi Shi, Shengli Cao, Wenzhi Guo, Shuijun Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	brain death renal injury pyroptosis caspase-1 caspase-11 hypoxia Surgery RD1-811
Acceso en línea:	https://doaj.org/article/3cac53ad661540d7b44127f4cbefa0f4
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spelling	oai:doaj.org-article:3cac53ad661540d7b44127f4cbefa0f42021-12-01T08:01:33ZCaspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney2296-875X10.3389/fsurg.2021.760989https://doaj.org/article/3cac53ad661540d7b44127f4cbefa0f42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fsurg.2021.760989/fullhttps://doaj.org/toc/2296-875XBrain death (BD) induces an organ-level inflammatory response. However, the underlying mechanisms have not been fully elucidated. Here, we investigated the role of caspase-1-mediated pyroptosis in BD-induced kidney injury in rats. A BD model was established in Sprague-Dawley rats. The rats were intravenously injected with Z-YVAD-FMK 1 h before BD, and sham-operated rats served as controls. After 0, 1, 2, 4, and 6 h of BD, renal injury, and renal expression of the nod-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, caspase-11, gasdermin D (GSDMD), IL-1β, and IL-18 were assessed using quantitative reverse transcriptase-polymerase chain reaction, western blotting, and immunohistochemistry. Blood urea nitrogen and serum creatinine levels were measured. Additionally, renal tubular epithelial cells (NRK-52E) were subjected to 3 h of hypoxia followed by 6 h of reoxygenation and incubated with Z-YVAD-FMK before hypoxia and reoxygenation. Caspase-11 was knocked-down using small interfering RNA technology. Cell viability and levels of pyroptosis-associated proteins were assessed thereafter. NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 expression levels were upregulated in BD rats. Treatment with Z-YVAD-FMK reduced mRNA and protein levels of caspase-1, GSDMD, IL-1β, and IL-18, improved renal function, and alleviated renal injury. Z-YVAD-FMK efficaciously reduced pyroptosis effects in kidneys in BD rats. Thus, it could be considered as a therapeutic target for BD-induced kidney injury.Weifeng LiuWeifeng LiuWeifeng LiuWeifeng LiuDongjing YangDongjing YangDongjing YangJihua ShiJihua ShiJihua ShiPeihao WenJiakai ZhangZhihui WangBowen HuXiaoyi ShiShengli CaoWenzhi GuoWenzhi GuoWenzhi GuoShuijun ZhangShuijun ZhangShuijun ZhangFrontiers Media S.A.articlebrain deathrenal injurypyroptosiscaspase-1caspase-11hypoxiaSurgeryRD1-811ENFrontiers in Surgery, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	brain death renal injury pyroptosis caspase-1 caspase-11 hypoxia Surgery RD1-811
spellingShingle	brain death renal injury pyroptosis caspase-1 caspase-11 hypoxia Surgery RD1-811 Weifeng Liu Weifeng Liu Weifeng Liu Weifeng Liu Dongjing Yang Dongjing Yang Dongjing Yang Jihua Shi Jihua Shi Jihua Shi Peihao Wen Jiakai Zhang Zhihui Wang Bowen Hu Xiaoyi Shi Shengli Cao Wenzhi Guo Wenzhi Guo Wenzhi Guo Shuijun Zhang Shuijun Zhang Shuijun Zhang Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney
description	Brain death (BD) induces an organ-level inflammatory response. However, the underlying mechanisms have not been fully elucidated. Here, we investigated the role of caspase-1-mediated pyroptosis in BD-induced kidney injury in rats. A BD model was established in Sprague-Dawley rats. The rats were intravenously injected with Z-YVAD-FMK 1 h before BD, and sham-operated rats served as controls. After 0, 1, 2, 4, and 6 h of BD, renal injury, and renal expression of the nod-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, caspase-11, gasdermin D (GSDMD), IL-1β, and IL-18 were assessed using quantitative reverse transcriptase-polymerase chain reaction, western blotting, and immunohistochemistry. Blood urea nitrogen and serum creatinine levels were measured. Additionally, renal tubular epithelial cells (NRK-52E) were subjected to 3 h of hypoxia followed by 6 h of reoxygenation and incubated with Z-YVAD-FMK before hypoxia and reoxygenation. Caspase-11 was knocked-down using small interfering RNA technology. Cell viability and levels of pyroptosis-associated proteins were assessed thereafter. NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 expression levels were upregulated in BD rats. Treatment with Z-YVAD-FMK reduced mRNA and protein levels of caspase-1, GSDMD, IL-1β, and IL-18, improved renal function, and alleviated renal injury. Z-YVAD-FMK efficaciously reduced pyroptosis effects in kidneys in BD rats. Thus, it could be considered as a therapeutic target for BD-induced kidney injury.
format	article
author	Weifeng Liu Weifeng Liu Weifeng Liu Weifeng Liu Dongjing Yang Dongjing Yang Dongjing Yang Jihua Shi Jihua Shi Jihua Shi Peihao Wen Jiakai Zhang Zhihui Wang Bowen Hu Xiaoyi Shi Shengli Cao Wenzhi Guo Wenzhi Guo Wenzhi Guo Shuijun Zhang Shuijun Zhang Shuijun Zhang
author_facet	Weifeng Liu Weifeng Liu Weifeng Liu Weifeng Liu Dongjing Yang Dongjing Yang Dongjing Yang Jihua Shi Jihua Shi Jihua Shi Peihao Wen Jiakai Zhang Zhihui Wang Bowen Hu Xiaoyi Shi Shengli Cao Wenzhi Guo Wenzhi Guo Wenzhi Guo Shuijun Zhang Shuijun Zhang Shuijun Zhang
author_sort	Weifeng Liu
title	Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney
title_short	Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney
title_full	Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney
title_fullStr	Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney
title_full_unstemmed	Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney
title_sort	caspase-1 inhibitor reduces pyroptosis induced by brain death in kidney
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3cac53ad661540d7b44127f4cbefa0f4
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Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney

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