Foodborne toxin Aflatoxin B_(1)induced glomerular podocyte inflammation through proteolysis of RelA,downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway  

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

机构地区：[1]School of Biology and Food Engineering,Changshu Institute of Technology,Suzhou 215500,China [2]Center for Clinical Mass Spectrometry,School of Pharmaceutical Sciences,Soochow University,Suzhou 215123,China [3]School of Food and Biological Engineering,Hefei University of Technology,Hefei 230009,China [4]MOE Joint International Research Laboratory of Animal Health and Food Safety,College of Veterinary Medicine,Nanjing Agricultural University,Nanjing 210095,China [5]Department of Chemistry,Faculty of Science,University of Hradec Kralove,Hradec Kralove 50003,Czech Republic [6]College of Life Science,Yangtze University,Jingzhou 434025,China [7]Wuxi Medical College,Jiangnan University,Wuxi 214122,China [8]Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch,Wuxi 214013,China

出　　处：《Food Science and Human Wellness》2024年第4期2289-2309,共21页食品科学与人类健康（英文）

基　　金：funded by Suzhou Science and Technology Council(SNG201907);Universities Natural Science Foundation of Jiangsu Province(20KJB330002);General Program of China Postdoctoral Science Foundation(2022M711369);the Startup Funding of Soochow University,Jiangsu Province-Suzhou Science and Technology Planning Project(SL T201917);National Natural Science Foundation of China(32172922,31972741);Natural Science Foundation of Jiangsu Province of China(BK20211216,BK20221091);the Startup Funding of Hefei University of Technology(1302003712022058);China-CEEC Joint University Education Project(202010);the Excellence Project PrF UHK(2217/2022-2023)。

摘　　要：Aflatoxin B_(1)(AFB_(1))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.AFB_(1)induces podocyte inflammation,proteinuria and renal dysfunction.Studying the mechanism of AFB_(1)-induced podocyte inflammation and murine kidney dysfunction,we detected that AFB_(1)increased ubiquitindependent 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 AFB_(1)-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 AFB_(1)-induced glomerular podocyte inflammation.Our study revealed a novel mechanism,via RelA,for the control of AFB_(1)’s nephrotoxicity,leading to an effective protection of food safety and public health.

关 键 词：Aflatoxin B_(1) Podocyte inflammation miRNA-9 Chemokine(C-X-C motif)receptor 4 RelA ubiquitin-dependent degradation 

分 类 号：TS201.6[轻工技术与工程—食品科学]