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Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer

Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD(+)-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific...

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Autores principales: Lo Sasso, Giuseppe, Ryu, Dongryeol, Mouchiroud, Laurent, Fernando, Samodha C., Anderson, Christopher L., Katsyuba, Elena, Piersigilli, Alessandra, Hottiger, Michael O., Schoonjans, Kristina, Auwerx, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094521/
https://www.ncbi.nlm.nih.gov/pubmed/25013930
http://dx.doi.org/10.1371/journal.pone.0102495
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author Lo Sasso, Giuseppe
Ryu, Dongryeol
Mouchiroud, Laurent
Fernando, Samodha C.
Anderson, Christopher L.
Katsyuba, Elena
Piersigilli, Alessandra
Hottiger, Michael O.
Schoonjans, Kristina
Auwerx, Johan
author_facet Lo Sasso, Giuseppe
Ryu, Dongryeol
Mouchiroud, Laurent
Fernando, Samodha C.
Anderson, Christopher L.
Katsyuba, Elena
Piersigilli, Alessandra
Hottiger, Michael O.
Schoonjans, Kristina
Auwerx, Johan
author_sort Lo Sasso, Giuseppe
collection PubMed
description Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD(+)-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1(int−/−)) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC.
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spelling pubmed-40945212014-07-15 Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer Lo Sasso, Giuseppe Ryu, Dongryeol Mouchiroud, Laurent Fernando, Samodha C. Anderson, Christopher L. Katsyuba, Elena Piersigilli, Alessandra Hottiger, Michael O. Schoonjans, Kristina Auwerx, Johan PLoS One Research Article Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD(+)-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1(int−/−)) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC. Public Library of Science 2014-07-11 /pmc/articles/PMC4094521/ /pubmed/25013930 http://dx.doi.org/10.1371/journal.pone.0102495 Text en © 2014 Lo Sasso et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lo Sasso, Giuseppe
Ryu, Dongryeol
Mouchiroud, Laurent
Fernando, Samodha C.
Anderson, Christopher L.
Katsyuba, Elena
Piersigilli, Alessandra
Hottiger, Michael O.
Schoonjans, Kristina
Auwerx, Johan
Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer
title Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer
title_full Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer
title_fullStr Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer
title_full_unstemmed Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer
title_short Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer
title_sort loss of sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094521/
https://www.ncbi.nlm.nih.gov/pubmed/25013930
http://dx.doi.org/10.1371/journal.pone.0102495
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