Quercetin alleviates acute kidney injury by inhibiting ferroptosis
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-oxidan...
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Format: | Article |
Language: | English |
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Elsevier
2021-02-01
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Series: | Journal of Advanced Research |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123220301661 |
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doaj-62b124d6e6a24a9898cbc73f0aed8e3b |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yue Wang Fei Quan Qiuhua Cao Yanting Lin Chongxiu Yue Ran Bi Xinmeng Cui Hongbao Yang Yong Yang Lutz Birnbaumer Xianjing Li Xinghua Gao |
spellingShingle |
Yue Wang Fei Quan Qiuhua Cao Yanting Lin Chongxiu Yue Ran Bi Xinmeng Cui Hongbao Yang Yong Yang Lutz Birnbaumer Xianjing Li Xinghua Gao Quercetin alleviates acute kidney injury by inhibiting ferroptosis Journal of Advanced Research Ferroptosis Quercetin Acute kidney injury Activation transcription factor 3 Macrophages |
author_facet |
Yue Wang Fei Quan Qiuhua Cao Yanting Lin Chongxiu Yue Ran Bi Xinmeng Cui Hongbao Yang Yong Yang Lutz Birnbaumer Xianjing Li Xinghua Gao |
author_sort |
Yue Wang |
title |
Quercetin alleviates acute kidney injury by inhibiting ferroptosis |
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 |
publisher |
Elsevier |
series |
Journal of Advanced Research |
issn |
2090-1232 |
publishDate |
2021-02-01 |
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. |
topic |
Ferroptosis Quercetin Acute kidney injury Activation transcription factor 3 Macrophages |
url |
http://www.sciencedirect.com/science/article/pii/S2090123220301661 |
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AT yuewang quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT feiquan quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT qiuhuacao quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT yantinglin quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT chongxiuyue quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT ranbi quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT xinmengcui quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT hongbaoyang quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT yongyang quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT lutzbirnbaumer quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT xianjingli quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis AT xinghuagao quercetinalleviatesacutekidneyinjurybyinhibitingferroptosis |
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doaj-62b124d6e6a24a9898cbc73f0aed8e3b2021-02-15T04:13:08ZengElsevierJournal of Advanced Research2090-12322021-02-0128231243Quercetin alleviates acute kidney injury by inhibiting ferroptosisYue Wang0Fei Quan1Qiuhua Cao2Yanting Lin3Chongxiu Yue4Ran Bi5Xinmeng Cui6Hongbao Yang7Yong Yang8Lutz Birnbaumer9Xianjing Li10Xinghua Gao11Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR ChinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR ChinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR ChinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR ChinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR ChinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR ChinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR ChinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR ChinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China; School of Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004, Jiangsu, PR ChinaNeurobiology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA; Institute of Biomedical Research (BIOMED), Catholic University of Argentina, Buenos Aires C1107AFF, ArgentinaCenter for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China; Corresponding authors.Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S2090123220301661FerroptosisQuercetinAcute kidney injuryActivation transcription factor 3Macrophages |