Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway

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外文摘要：Aflatoxin B1(AFB1)is a naturally-occurring mycotoxin and recognized as the most toxic foodborne toxin,particularly causing damages to kidney.Glomerular podocytes are terminally differentiated epithelial cells.AFB1 induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB1-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB,increased ubiquitin-dependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitin ligase tripartite motif containing 7(TRIM7)in mouse podocyte clone-5(MPC-5)and mouse glomeruli.Reduction of RelA resulted in decreasing microRNA-9(miR-9)and activating the chemokine receptor 4(CXCR4),thioredoxin interacting protein(TXNIP),and NOD-like receptor pyrin domain-containing 3(NLRP3)signaling axis(CXCR4/TXNIP/NLRP3 pathway),leading to podocyte inflammation.We also determined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3 pathway activation.Overexpression of miR-9 or deletion of CXCR4 suppressed AFB1-induced CXCR4/TXNIP/NLRP3 pathway,resulting in alleviating podocyte inflammation and kidney dysfunction.Our findings indicated that ubiquitin-dependent proteolysis of RelA,downregulation of miR-9,and activation of CXCR4/TXNIP/NLRP3 pathway played an essential role in AFB1-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB1's nephrotoxicity,leading to an effective protection of food safety and public health.

外文关键词：

Aflatoxin B1Podocyte inflammationmiRNA-9Chemokine(C-X-C motif)receptor 4RelA ubiquitin-dependent degradation

作者：

Jie Zhang、Shuang Yang、Baocai Xu、Zihui Qin、Xinyi Guo、Ben Wei、Qinghua Wu、Kamil Kuca、Tushuai Li、Wenda Wu

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作者单位：

School of Biology and Food Engineering,Changshu Institute of Technology,Suzhou 215500,China

Center for Clinical Mass Spectrometry,School of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China

School of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,China

MOE Joint International Research Laboratory of Animal Health and Food Safety,College of Veterinary Medicine,Nanjing Agricultural University,Nanjing 210095,China

Department of Chemistry,Faculty of Science,University of Hradec Kralove,Hradec Kralove 50003,Czech Republic

College of Life Science,Yangtze University,Jingzhou 434025,China

Wuxi Medical College,Jiangnan University,Wuxi 214122,China

Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch,Wuxi 214013,China

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基金：

Suzhou Science and Technology CouncilUniversities Natural Science Foundation of Jiangsu ProvinceGeneral Program of China Postdoctoral Science FoundationStartup Funding of Soochow University,Jiangsu Province-Suzhou Science and Technology Planning Project国家自然科学基金国家自然科学基金江苏省自然科学基金江苏省自然科学基金Startup Funding of Hefei University of TechnologyChina-CEEC Joint University Education ProjectExcellence Project PrF UHK

项目编号：

SNG20190720KJB3300022022M711369SL T2019173217292231972741BK20211216BK2022109113020-037120220582020102217/2022-2023

出版年：

2024

DOI：

10.26599/FSHW.2022.9250191

食品科学与人类健康(英文)

CSTPCD

ISSN：

年,卷(期)：2024.13(4)

参考文献量65