Quercetin alleviates acute kidney injury by inhibiting ferroptosis

Autores
Wang, Yuemin; Quan, Fei; Cao, Qiuhua; Lin, Yanting; Yue, Chongxiu; Bi, Ran; Cui, Xinmeng; Yang, Hongbao; Yang, Yong; Birnbaumer, Lutz; Li, Xianjing; Gao, Xinghua
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction: Ferroptosis is an iron-dependent regulated necrosis and has been proven to contribute to the progress of acute kidney injury (AKI). Quercetin (QCT), a natural flavonoid which is commonly found in numerous fruits and vegetables, has extensive pharmacological effects, such as anti-oxidant, anti-inflammatory and anti-senescence effects. Objectives: This study aims to explain whether ferroptosis is a therapeutic strategy to AKI, and to explore the effect of QCT on AKI ferroptosis. Methods: NRK-52E cells and HK-2 cells were used for in vitro ferroptosis studies. Morphology of cells was detected by transmission electron microscopy. Lipid ROS was assayed using flow cytometry. In vivo, AKI was induced by ischemia–reperfusion (I/R) or folic acid (FA). To explore the molecular mechanisms, RNA-sequence analysis was performed. Transwell was used to detect macrophage migration. Results: We discovered that quercetin (QCT), a natural flavonoid, inhibited ferroptosis in renal proximal tubular epithelial cells. QCT blocked the typical morphologic changes of ferroptotic cells by reducing the levels of malondialdehyde (MDA) and lipid ROS and increasing the levels of glutathione (GSH). Moreover, QCT ameliorated AKI induced by I/R or FA. RNA-sequence analysis highlighted activation transcription factor 3 (ATF3), as it was the dominant one among all the 299 down-regulated genes by QCT. Knockdown of ATF3 could significantly increase the levels of SLC7A11, GPX4 and increased the cell viability. In addition, ferroptotic cells were found to be extremely pro-inflammatory by recruiting macrophages through CCL2, while QCT inhibited the chemotaxis of macrophages induced by ferroptosis in AKI. Conclusions: Collectively, these results identify QCT as a ferroptosis inhibitor and provide new therapeutic strategies for diseases related to ferroptosis.
Fil: Wang, Yuemin. China Pharmaceutical University; China
Fil: Quan, Fei. China Pharmaceutical University; China
Fil: Cao, Qiuhua. China Pharmaceutical University; China
Fil: Lin, Yanting. China Pharmaceutical University; China
Fil: Yue, Chongxiu. China Pharmaceutical University; China
Fil: Bi, Ran. China Pharmaceutical University; China
Fil: Cui, Xinmeng. China Pharmaceutical University; China
Fil: Yang, Hongbao. China Pharmaceutical University; China
Fil: Yang, Yong. China Pharmaceutical University; China. Xuzhou Medical University; China
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Li, Xianjing. China Pharmaceutical University; China
Fil: Gao, Xinghua. China Pharmaceutical University; China
Materia
ACTIVATION TRANSCRIPTION FACTOR 3
ACUTE KIDNEY INJURY
FERROPTOSIS
MACROPHAGES
QUERCETIN
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/170218
Acceder
id CONICETDig_626d58839428a5bb72e7b896692dd037
oai_identifier_str oai:ri.conicet.gov.ar:11336/170218
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Quercetin alleviates acute kidney injury by inhibiting ferroptosisWang, YueminQuan, FeiCao, QiuhuaLin, YantingYue, ChongxiuBi, RanCui, XinmengYang, HongbaoYang, YongBirnbaumer, LutzLi, XianjingGao, XinghuaACTIVATION TRANSCRIPTION FACTOR 3ACUTE KIDNEY INJURYFERROPTOSISMACROPHAGESQUERCETINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Introduction: Ferroptosis is an iron-dependent regulated necrosis and has been proven to contribute to the progress of acute kidney injury (AKI). Quercetin (QCT), a natural flavonoid which is commonly found in numerous fruits and vegetables, has extensive pharmacological effects, such as anti-oxidant, anti-inflammatory and anti-senescence effects. Objectives: This study aims to explain whether ferroptosis is a therapeutic strategy to AKI, and to explore the effect of QCT on AKI ferroptosis. Methods: NRK-52E cells and HK-2 cells were used for in vitro ferroptosis studies. Morphology of cells was detected by transmission electron microscopy. Lipid ROS was assayed using flow cytometry. In vivo, AKI was induced by ischemia–reperfusion (I/R) or folic acid (FA). To explore the molecular mechanisms, RNA-sequence analysis was performed. Transwell was used to detect macrophage migration. Results: We discovered that quercetin (QCT), a natural flavonoid, inhibited ferroptosis in renal proximal tubular epithelial cells. QCT blocked the typical morphologic changes of ferroptotic cells by reducing the levels of malondialdehyde (MDA) and lipid ROS and increasing the levels of glutathione (GSH). Moreover, QCT ameliorated AKI induced by I/R or FA. RNA-sequence analysis highlighted activation transcription factor 3 (ATF3), as it was the dominant one among all the 299 down-regulated genes by QCT. Knockdown of ATF3 could significantly increase the levels of SLC7A11, GPX4 and increased the cell viability. In addition, ferroptotic cells were found to be extremely pro-inflammatory by recruiting macrophages through CCL2, while QCT inhibited the chemotaxis of macrophages induced by ferroptosis in AKI. Conclusions: Collectively, these results identify QCT as a ferroptosis inhibitor and provide new therapeutic strategies for diseases related to ferroptosis.Fil: Wang, Yuemin. China Pharmaceutical University; ChinaFil: Quan, Fei. China Pharmaceutical University; ChinaFil: Cao, Qiuhua. China Pharmaceutical University; ChinaFil: Lin, Yanting. China Pharmaceutical University; ChinaFil: Yue, Chongxiu. China Pharmaceutical University; ChinaFil: Bi, Ran. China Pharmaceutical University; ChinaFil: Cui, Xinmeng. China Pharmaceutical University; ChinaFil: Yang, Hongbao. China Pharmaceutical University; ChinaFil: Yang, Yong. China Pharmaceutical University; China. Xuzhou Medical University; ChinaFil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Li, Xianjing. China Pharmaceutical University; ChinaFil: Gao, Xinghua. China Pharmaceutical University; ChinaElsevier2021-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/170218Wang, Yuemin; Quan, Fei; Cao, Qiuhua; Lin, Yanting; Yue, Chongxiu; et al.; Quercetin alleviates acute kidney injury by inhibiting ferroptosis; Elsevier; Journal of Advanced Research; 28; 2-2021; 231-2432090-1232CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.jare.2020.07.007info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2090123220301661?via%3Dihubinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:19Zoai:ri.conicet.gov.ar:11336/170218instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:08:20.169CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Quercetin alleviates acute kidney injury by inhibiting ferroptosis
title Quercetin alleviates acute kidney injury by inhibiting ferroptosis
spellingShingle Quercetin alleviates acute kidney injury by inhibiting ferroptosis
Wang, Yuemin
ACTIVATION TRANSCRIPTION FACTOR 3
ACUTE KIDNEY INJURY
FERROPTOSIS
MACROPHAGES
QUERCETIN
title_short Quercetin alleviates acute kidney injury by inhibiting ferroptosis
title_full Quercetin alleviates acute kidney injury by inhibiting ferroptosis
title_fullStr Quercetin alleviates acute kidney injury by inhibiting ferroptosis
title_full_unstemmed Quercetin alleviates acute kidney injury by inhibiting ferroptosis
title_sort Quercetin alleviates acute kidney injury by inhibiting ferroptosis
dc.creator.none.fl_str_mv Wang, Yuemin
Quan, Fei
Cao, Qiuhua
Lin, Yanting
Yue, Chongxiu
Bi, Ran
Cui, Xinmeng
Yang, Hongbao
Yang, Yong
Birnbaumer, Lutz
Li, Xianjing
Gao, Xinghua
author Wang, Yuemin
author_facet Wang, Yuemin
Quan, Fei
Cao, Qiuhua
Lin, Yanting
Yue, Chongxiu
Bi, Ran
Cui, Xinmeng
Yang, Hongbao
Yang, Yong
Birnbaumer, Lutz
Li, Xianjing
Gao, Xinghua
author_role author
author2 Quan, Fei
Cao, Qiuhua
Lin, Yanting
Yue, Chongxiu
Bi, Ran
Cui, Xinmeng
Yang, Hongbao
Yang, Yong
Birnbaumer, Lutz
Li, Xianjing
Gao, Xinghua
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTIVATION TRANSCRIPTION FACTOR 3
ACUTE KIDNEY INJURY
FERROPTOSIS
MACROPHAGES
QUERCETIN
topic ACTIVATION TRANSCRIPTION FACTOR 3
ACUTE KIDNEY INJURY
FERROPTOSIS
MACROPHAGES
QUERCETIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Introduction: Ferroptosis is an iron-dependent regulated necrosis and has been proven to contribute to the progress of acute kidney injury (AKI). Quercetin (QCT), a natural flavonoid which is commonly found in numerous fruits and vegetables, has extensive pharmacological effects, such as anti-oxidant, anti-inflammatory and anti-senescence effects. Objectives: This study aims to explain whether ferroptosis is a therapeutic strategy to AKI, and to explore the effect of QCT on AKI ferroptosis. Methods: NRK-52E cells and HK-2 cells were used for in vitro ferroptosis studies. Morphology of cells was detected by transmission electron microscopy. Lipid ROS was assayed using flow cytometry. In vivo, AKI was induced by ischemia–reperfusion (I/R) or folic acid (FA). To explore the molecular mechanisms, RNA-sequence analysis was performed. Transwell was used to detect macrophage migration. Results: We discovered that quercetin (QCT), a natural flavonoid, inhibited ferroptosis in renal proximal tubular epithelial cells. QCT blocked the typical morphologic changes of ferroptotic cells by reducing the levels of malondialdehyde (MDA) and lipid ROS and increasing the levels of glutathione (GSH). Moreover, QCT ameliorated AKI induced by I/R or FA. RNA-sequence analysis highlighted activation transcription factor 3 (ATF3), as it was the dominant one among all the 299 down-regulated genes by QCT. Knockdown of ATF3 could significantly increase the levels of SLC7A11, GPX4 and increased the cell viability. In addition, ferroptotic cells were found to be extremely pro-inflammatory by recruiting macrophages through CCL2, while QCT inhibited the chemotaxis of macrophages induced by ferroptosis in AKI. Conclusions: Collectively, these results identify QCT as a ferroptosis inhibitor and provide new therapeutic strategies for diseases related to ferroptosis.
Fil: Wang, Yuemin. China Pharmaceutical University; China
Fil: Quan, Fei. China Pharmaceutical University; China
Fil: Cao, Qiuhua. China Pharmaceutical University; China
Fil: Lin, Yanting. China Pharmaceutical University; China
Fil: Yue, Chongxiu. China Pharmaceutical University; China
Fil: Bi, Ran. China Pharmaceutical University; China
Fil: Cui, Xinmeng. China Pharmaceutical University; China
Fil: Yang, Hongbao. China Pharmaceutical University; China
Fil: Yang, Yong. China Pharmaceutical University; China. Xuzhou Medical University; China
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Li, Xianjing. China Pharmaceutical University; China
Fil: Gao, Xinghua. China Pharmaceutical University; China
description Introduction: Ferroptosis is an iron-dependent regulated necrosis and has been proven to contribute to the progress of acute kidney injury (AKI). Quercetin (QCT), a natural flavonoid which is commonly found in numerous fruits and vegetables, has extensive pharmacological effects, such as anti-oxidant, anti-inflammatory and anti-senescence effects. Objectives: This study aims to explain whether ferroptosis is a therapeutic strategy to AKI, and to explore the effect of QCT on AKI ferroptosis. Methods: NRK-52E cells and HK-2 cells were used for in vitro ferroptosis studies. Morphology of cells was detected by transmission electron microscopy. Lipid ROS was assayed using flow cytometry. In vivo, AKI was induced by ischemia–reperfusion (I/R) or folic acid (FA). To explore the molecular mechanisms, RNA-sequence analysis was performed. Transwell was used to detect macrophage migration. Results: We discovered that quercetin (QCT), a natural flavonoid, inhibited ferroptosis in renal proximal tubular epithelial cells. QCT blocked the typical morphologic changes of ferroptotic cells by reducing the levels of malondialdehyde (MDA) and lipid ROS and increasing the levels of glutathione (GSH). Moreover, QCT ameliorated AKI induced by I/R or FA. RNA-sequence analysis highlighted activation transcription factor 3 (ATF3), as it was the dominant one among all the 299 down-regulated genes by QCT. Knockdown of ATF3 could significantly increase the levels of SLC7A11, GPX4 and increased the cell viability. In addition, ferroptotic cells were found to be extremely pro-inflammatory by recruiting macrophages through CCL2, while QCT inhibited the chemotaxis of macrophages induced by ferroptosis in AKI. Conclusions: Collectively, these results identify QCT as a ferroptosis inhibitor and provide new therapeutic strategies for diseases related to ferroptosis.
publishDate 2021
dc.date.none.fl_str_mv 2021-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/170218
Wang, Yuemin; Quan, Fei; Cao, Qiuhua; Lin, Yanting; Yue, Chongxiu; et al.; Quercetin alleviates acute kidney injury by inhibiting ferroptosis; Elsevier; Journal of Advanced Research; 28; 2-2021; 231-243
2090-1232
CONICET Digital
CONICET
url http://hdl.handle.net/11336/170218
identifier_str_mv Wang, Yuemin; Quan, Fei; Cao, Qiuhua; Lin, Yanting; Yue, Chongxiu; et al.; Quercetin alleviates acute kidney injury by inhibiting ferroptosis; Elsevier; Journal of Advanced Research; 28; 2-2021; 231-243
2090-1232
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jare.2020.07.007
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2090123220301661?via%3Dihub
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842270040577015808
score 13.13397

Publicaciones similares