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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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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. |
format | Online Article Text |
id | pubmed-4094521 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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