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Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice

Increasing evidence shows the essential participation of gut microbiota in human health and diseases by shaping local and systemic immunity. Despite an accumulating body of studies showing that chronic kidney disease (CKD) is closely associated with disturbances in the composition of gut microbiota,...

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Autores principales: Watanabe, Ingrid Kazue Mizuno, Andrade-Silva, Magaiver, Foresto-Neto, Orestes, Felizardo, Raphael José Ferreira, Matheus, Marco Aurélio Costa, Silva, Reinaldo Correa, Cenedeze, Marcos Antônio, Honda, Tâmisa Seeko Bandeira, Perandini, Luiz Augusto Buoro, Volpini, Rildo Aparecido, Pacheco-Silva, Alvaro, Câmara, Niels Olsen Saraiva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783078/
https://www.ncbi.nlm.nih.gov/pubmed/33414781
http://dx.doi.org/10.3389/fimmu.2020.578623
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author Watanabe, Ingrid Kazue Mizuno
Andrade-Silva, Magaiver
Foresto-Neto, Orestes
Felizardo, Raphael José Ferreira
Matheus, Marco Aurélio Costa
Silva, Reinaldo Correa
Cenedeze, Marcos Antônio
Honda, Tâmisa Seeko Bandeira
Perandini, Luiz Augusto Buoro
Volpini, Rildo Aparecido
Pacheco-Silva, Alvaro
Câmara, Niels Olsen Saraiva
author_facet Watanabe, Ingrid Kazue Mizuno
Andrade-Silva, Magaiver
Foresto-Neto, Orestes
Felizardo, Raphael José Ferreira
Matheus, Marco Aurélio Costa
Silva, Reinaldo Correa
Cenedeze, Marcos Antônio
Honda, Tâmisa Seeko Bandeira
Perandini, Luiz Augusto Buoro
Volpini, Rildo Aparecido
Pacheco-Silva, Alvaro
Câmara, Niels Olsen Saraiva
author_sort Watanabe, Ingrid Kazue Mizuno
collection PubMed
description Increasing evidence shows the essential participation of gut microbiota in human health and diseases by shaping local and systemic immunity. Despite an accumulating body of studies showing that chronic kidney disease (CKD) is closely associated with disturbances in the composition of gut microbiota, it remains unclear the importance of gut microbiota in the onset and development of CKD. For the purpose of untangling the role of gut microbiota in CKD, gut microbiota was depleted with a pool of broad-spectrum antibiotics in mice submitted to unilateral ureteral obstruction (UUO). Depletion of gut microbiota significantly decreased levels of proinflammatory cytokines and fibrosis markers, attenuating renal injury. Additionally, to study whether the pathogenic role of gut microbiota is dependent of microbial-host crosstalk, we generated mice lacking Myd88 (myeloid differentiation primary response gene 8) expression in intestinal epithelial cells (IECs) and performed UUO. The absence of Myd88 in IECs prevented a bacterial burden in mesenteric lymph nodes as observed in WT mice after UUO and led to lower expression of proinflammatory cytokines and chemokines, reducing deposition of type I collagen and, ultimately, attenuating renal damage. Therefore, our results suggest that the presence of gut microbiota is crucial for the development of CKD and may be dependent of Myd88 signaling in IECs, which appears to be essential to maturation of immune cells intimately involved in aggravation of inflammatory scenarios.
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spelling pubmed-77830782021-01-06 Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice Watanabe, Ingrid Kazue Mizuno Andrade-Silva, Magaiver Foresto-Neto, Orestes Felizardo, Raphael José Ferreira Matheus, Marco Aurélio Costa Silva, Reinaldo Correa Cenedeze, Marcos Antônio Honda, Tâmisa Seeko Bandeira Perandini, Luiz Augusto Buoro Volpini, Rildo Aparecido Pacheco-Silva, Alvaro Câmara, Niels Olsen Saraiva Front Immunol Immunology Increasing evidence shows the essential participation of gut microbiota in human health and diseases by shaping local and systemic immunity. Despite an accumulating body of studies showing that chronic kidney disease (CKD) is closely associated with disturbances in the composition of gut microbiota, it remains unclear the importance of gut microbiota in the onset and development of CKD. For the purpose of untangling the role of gut microbiota in CKD, gut microbiota was depleted with a pool of broad-spectrum antibiotics in mice submitted to unilateral ureteral obstruction (UUO). Depletion of gut microbiota significantly decreased levels of proinflammatory cytokines and fibrosis markers, attenuating renal injury. Additionally, to study whether the pathogenic role of gut microbiota is dependent of microbial-host crosstalk, we generated mice lacking Myd88 (myeloid differentiation primary response gene 8) expression in intestinal epithelial cells (IECs) and performed UUO. The absence of Myd88 in IECs prevented a bacterial burden in mesenteric lymph nodes as observed in WT mice after UUO and led to lower expression of proinflammatory cytokines and chemokines, reducing deposition of type I collagen and, ultimately, attenuating renal damage. Therefore, our results suggest that the presence of gut microbiota is crucial for the development of CKD and may be dependent of Myd88 signaling in IECs, which appears to be essential to maturation of immune cells intimately involved in aggravation of inflammatory scenarios. Frontiers Media S.A. 2020-12-22 /pmc/articles/PMC7783078/ /pubmed/33414781 http://dx.doi.org/10.3389/fimmu.2020.578623 Text en Copyright © 2020 Watanabe, Andrade-Silva, Foresto-Neto, Felizardo, Matheus, Silva, Cenedeze, Honda, Perandini, Volpini, Pacheco-Silva and Câmara http://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 Immunology
Watanabe, Ingrid Kazue Mizuno
Andrade-Silva, Magaiver
Foresto-Neto, Orestes
Felizardo, Raphael José Ferreira
Matheus, Marco Aurélio Costa
Silva, Reinaldo Correa
Cenedeze, Marcos Antônio
Honda, Tâmisa Seeko Bandeira
Perandini, Luiz Augusto Buoro
Volpini, Rildo Aparecido
Pacheco-Silva, Alvaro
Câmara, Niels Olsen Saraiva
Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice
title Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice
title_full Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice
title_fullStr Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice
title_full_unstemmed Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice
title_short Gut Microbiota and Intestinal Epithelial Myd88 Signaling Are Crucial for Renal Injury in UUO Mice
title_sort gut microbiota and intestinal epithelial myd88 signaling are crucial for renal injury in uuo mice
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783078/
https://www.ncbi.nlm.nih.gov/pubmed/33414781
http://dx.doi.org/10.3389/fimmu.2020.578623
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