Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway
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 me...
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Tsinghua University Press
2024-07-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2022.9250191 |
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| author | Jie Zhang Shuang Yang Baocai Xu Zihui Qin Xinyi Guo Ben Wei Qinghua Wu Kamil Kuca Tushuai Li Wenda Wu |
| author_facet | Jie Zhang Shuang Yang Baocai Xu Zihui Qin Xinyi Guo Ben Wei Qinghua Wu Kamil Kuca Tushuai Li Wenda Wu |
| author_sort | Jie Zhang |
| collection | DOAJ |
| description | 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 AFB1 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. |
| format | Article |
| id | doaj-art-682321efc31044a39889e69c00cedeb6 |
| institution | Kabale University |
| issn | 2097-0765 2213-4530 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-682321efc31044a39889e69c00cedeb62025-01-10T06:56:48ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-07-011342289230910.26599/FSHW.2022.9250191Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathwayJie Zhang0Shuang Yang1Baocai Xu2Zihui Qin3Xinyi Guo4Ben Wei5Qinghua Wu6Kamil Kuca7Tushuai Li8Wenda Wu9School of Biology and Food Engineering, Changshu Institute of Technology, Suzhou 215500, ChinaCenter for Clinical Mass Spectrometry, School of Pharmaceutical Sciences, Soochow University, Suzhou 215123, ChinaSchool of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaSchool of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaSchool of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaSchool of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaDepartment of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove 50003, Czech RepublicDepartment of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove 50003, Czech RepublicWuxi Medical College, Jiangnan University, Wuxi 214122, ChinaSchool of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, ChinaAflatoxin 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 AFB1 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.https://www.sciopen.com/article/10.26599/FSHW.2022.9250191afl atoxin b1podocyte infl ammationmirna-9chemokine (c-x-c motif) receptor 4rela ubiquitin-dependent degradation |
| spellingShingle | Jie Zhang Shuang Yang Baocai Xu Zihui Qin Xinyi Guo Ben Wei Qinghua Wu Kamil Kuca Tushuai Li Wenda Wu Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway Food Science and Human Wellness afl atoxin b1 podocyte infl ammation mirna-9 chemokine (c-x-c motif) receptor 4 rela ubiquitin-dependent degradation |
| title | Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway |
| title_full | Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway |
| title_fullStr | Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway |
| title_full_unstemmed | Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway |
| title_short | Foodborne toxin Aflatoxin B1 induced glomerular podocyte inflammation through proteolysis of RelA, downregulation of miR-9 and CXCR4/TXNIP/NLRP3 pathway |
| title_sort | foodborne toxin aflatoxin b1 induced glomerular podocyte inflammation through proteolysis of rela downregulation of mir 9 and cxcr4 txnip nlrp3 pathway |
| topic | afl atoxin b1 podocyte infl ammation mirna-9 chemokine (c-x-c motif) receptor 4 rela ubiquitin-dependent degradation |
| url | https://www.sciopen.com/article/10.26599/FSHW.2022.9250191 |
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