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Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction

Renal fibrosis contributes to kidney dysfunction in various chronic kidney diseases (CKDs). Renal fibrosis can be driven by renal tubular cell death and inflammation. Deletion of gasdermin E (GSDME), an executor of pyroptosis, has been reported to suppress renal tubular cell pyroptosis in several mo...

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Autores principales: Wu, Mengying, Xia, Weiwei, Jin, Qianqian, Zhou, Anning, Wang, Qian, Li, Shuzhen, Huang, Songming, Zhang, Aihua, Zhang, Yue, Li, Yuanyuan, Jia, Zhanjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567074/
https://www.ncbi.nlm.nih.gov/pubmed/34746148
http://dx.doi.org/10.3389/fcell.2021.754134
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author Wu, Mengying
Xia, Weiwei
Jin, Qianqian
Zhou, Anning
Wang, Qian
Li, Shuzhen
Huang, Songming
Zhang, Aihua
Zhang, Yue
Li, Yuanyuan
Jia, Zhanjun
author_facet Wu, Mengying
Xia, Weiwei
Jin, Qianqian
Zhou, Anning
Wang, Qian
Li, Shuzhen
Huang, Songming
Zhang, Aihua
Zhang, Yue
Li, Yuanyuan
Jia, Zhanjun
author_sort Wu, Mengying
collection PubMed
description Renal fibrosis contributes to kidney dysfunction in various chronic kidney diseases (CKDs). Renal fibrosis can be driven by renal tubular cell death and inflammation. Deletion of gasdermin E (GSDME), an executor of pyroptosis, has been reported to suppress renal tubular cell pyroptosis in several models of kidney injury. However, additional evidence confirming the role of GSDME in regulating renal fibrosis and kidney function in different CKDs is required. In our study, N-GSDME expression was significantly elevated in CKD models in vivo and in vitro. GSDME deletion alleviated renal fibrosis and inflammation in both unilateral ureteral ligation (UUO) and 5/6 nephrectomy (5/6Nx) models along with the attenuation of renal dysfunction. N-GSDME overexpression had a detrimental effect on fibrotic responses in UUO kidneys and TGF-β1-treated renal tubular epithelial cells. In addition, administration of caspase-3 inhibitor Z-DEVD-FMK, which inhibits caspase-3-mediated GSDME cleavage, protected against renal fibrosis both in vivo and in vitro. Collectively, these results provide evidence that the activation of GSDME is critical in regulating both renal fibrosis and kidney dysfunction possibly via promoting inflammatory responses in CKD. These findings may offer new insights into the identification of new therapeutic targets for protecting against CKDs.
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spelling pubmed-85670742021-11-05 Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction Wu, Mengying Xia, Weiwei Jin, Qianqian Zhou, Anning Wang, Qian Li, Shuzhen Huang, Songming Zhang, Aihua Zhang, Yue Li, Yuanyuan Jia, Zhanjun Front Cell Dev Biol Cell and Developmental Biology Renal fibrosis contributes to kidney dysfunction in various chronic kidney diseases (CKDs). Renal fibrosis can be driven by renal tubular cell death and inflammation. Deletion of gasdermin E (GSDME), an executor of pyroptosis, has been reported to suppress renal tubular cell pyroptosis in several models of kidney injury. However, additional evidence confirming the role of GSDME in regulating renal fibrosis and kidney function in different CKDs is required. In our study, N-GSDME expression was significantly elevated in CKD models in vivo and in vitro. GSDME deletion alleviated renal fibrosis and inflammation in both unilateral ureteral ligation (UUO) and 5/6 nephrectomy (5/6Nx) models along with the attenuation of renal dysfunction. N-GSDME overexpression had a detrimental effect on fibrotic responses in UUO kidneys and TGF-β1-treated renal tubular epithelial cells. In addition, administration of caspase-3 inhibitor Z-DEVD-FMK, which inhibits caspase-3-mediated GSDME cleavage, protected against renal fibrosis both in vivo and in vitro. Collectively, these results provide evidence that the activation of GSDME is critical in regulating both renal fibrosis and kidney dysfunction possibly via promoting inflammatory responses in CKD. These findings may offer new insights into the identification of new therapeutic targets for protecting against CKDs. Frontiers Media S.A. 2021-10-21 /pmc/articles/PMC8567074/ /pubmed/34746148 http://dx.doi.org/10.3389/fcell.2021.754134 Text en Copyright © 2021 Wu, Xia, Jin, Zhou, Wang, Li, Huang, Zhang, Zhang, Li and Jia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Wu, Mengying
Xia, Weiwei
Jin, Qianqian
Zhou, Anning
Wang, Qian
Li, Shuzhen
Huang, Songming
Zhang, Aihua
Zhang, Yue
Li, Yuanyuan
Jia, Zhanjun
Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction
title Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction
title_full Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction
title_fullStr Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction
title_full_unstemmed Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction
title_short Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction
title_sort gasdermin e deletion attenuates ureteral obstruction- and 5/6 nephrectomy-induced renal fibrosis and kidney dysfunction
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567074/
https://www.ncbi.nlm.nih.gov/pubmed/34746148
http://dx.doi.org/10.3389/fcell.2021.754134
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