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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F24%3A50021494" target="_blank" >RIV/62690094:18470/24:50021494 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S2213453024000995" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2213453024000995</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.26599/FSHW.2022.9250191" target="_blank" >10.26599/FSHW.2022.9250191</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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 ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitinligase 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 alsodetermined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3pathway 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 findingsindicated 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. Ourstudy revealed a novel mechanism, via RelA, for the control of AFB1’s nephrotoxicity, leading to an effectiveprotection of food safety and public health.

Název v anglickém jazyce

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

Popis výsledku anglicky

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 ubiquitindependent degradation of the transcription factor RelA through enhanced interaction of RelA with E3 ubiquitinligase 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 alsodetermined that downregulation of miR-9 led to CXCR4 expression and the downstream TXNIP/NLRP3pathway 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 findingsindicated 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. Ourstudy revealed a novel mechanism, via RelA, for the control of AFB1’s nephrotoxicity, leading to an effectiveprotection of food safety and public health.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Food Science and Human Wellness

ISSN

2097-0765

e-ISSN

2213-4530

Svazek periodika

13

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CN - Čínská lidová republika

Počet stran výsledku

21

Strana od-do

2289-2309

Kód UT WoS článku

001237320000002

EID výsledku v databázi Scopus

2-s2.0-85194238145