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Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression

There is increasing evidence that members of the gut microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with Crohn’s disease (CD), but the specific mechanism by which F. nucleatum promotes CD development is unclear. Here, we first examined the abundance of F. nucleatum and...

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Autores principales: Cao, Pan, Chen, Yongyu, Guo, Xufeng, Chen, Yan, Su, Wenhao, Zhan, Na, Dong, Weiguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047714/
https://www.ncbi.nlm.nih.gov/pubmed/32153411
http://dx.doi.org/10.3389/fphar.2020.00106
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author Cao, Pan
Chen, Yongyu
Guo, Xufeng
Chen, Yan
Su, Wenhao
Zhan, Na
Dong, Weiguo
author_facet Cao, Pan
Chen, Yongyu
Guo, Xufeng
Chen, Yan
Su, Wenhao
Zhan, Na
Dong, Weiguo
author_sort Cao, Pan
collection PubMed
description There is increasing evidence that members of the gut microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with Crohn’s disease (CD), but the specific mechanism by which F. nucleatum promotes CD development is unclear. Here, we first examined the abundance of F. nucleatum and its effects on CD disease activity and explored whether F. nucleatum aggravated intestinal inflammation and promoted intestinal mucosal barrier damage in vitro and in vivo. Our data showed that F. nucleatum was enriched in 41.21% of CD tissues from patients and was correlated with the clinical course, clinical activity, and refractory behavior of CD (P < 0.05). In addition, we found that F. nucleatum infection is involved in activating the endoplasmic reticulum stress (ERS) pathway during CD development to promote intestinal mucosal barrier destruction. Mechanistically, F. nucleatum targeted caspase activation and recruitment domain 3 (CARD3) to activate the ERS pathway and promote F. nucleatum-mediated mucosal barrier damage in vivo and in vitro. Thus, F. nucleatum coordinates a molecular network involving CARD3 and ERS to control the CD process. Measuring and targeting F. nucleatum and its associated pathways will provide valuable insight into the prevention and treatment of CD.
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spelling pubmed-70477142020-03-09 Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression Cao, Pan Chen, Yongyu Guo, Xufeng Chen, Yan Su, Wenhao Zhan, Na Dong, Weiguo Front Pharmacol Pharmacology There is increasing evidence that members of the gut microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with Crohn’s disease (CD), but the specific mechanism by which F. nucleatum promotes CD development is unclear. Here, we first examined the abundance of F. nucleatum and its effects on CD disease activity and explored whether F. nucleatum aggravated intestinal inflammation and promoted intestinal mucosal barrier damage in vitro and in vivo. Our data showed that F. nucleatum was enriched in 41.21% of CD tissues from patients and was correlated with the clinical course, clinical activity, and refractory behavior of CD (P < 0.05). In addition, we found that F. nucleatum infection is involved in activating the endoplasmic reticulum stress (ERS) pathway during CD development to promote intestinal mucosal barrier destruction. Mechanistically, F. nucleatum targeted caspase activation and recruitment domain 3 (CARD3) to activate the ERS pathway and promote F. nucleatum-mediated mucosal barrier damage in vivo and in vitro. Thus, F. nucleatum coordinates a molecular network involving CARD3 and ERS to control the CD process. Measuring and targeting F. nucleatum and its associated pathways will provide valuable insight into the prevention and treatment of CD. Frontiers Media S.A. 2020-02-21 /pmc/articles/PMC7047714/ /pubmed/32153411 http://dx.doi.org/10.3389/fphar.2020.00106 Text en Copyright © 2020 Cao, Chen, Guo, Chen, Su, Zhan and Dong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Cao, Pan
Chen, Yongyu
Guo, Xufeng
Chen, Yan
Su, Wenhao
Zhan, Na
Dong, Weiguo
Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression
title Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression
title_full Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression
title_fullStr Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression
title_full_unstemmed Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression
title_short Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression
title_sort fusobacterium nucleatum activates endoplasmic reticulum stress to promote crohn’s disease development via the upregulation of card3 expression
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047714/
https://www.ncbi.nlm.nih.gov/pubmed/32153411
http://dx.doi.org/10.3389/fphar.2020.00106
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