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Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer
- Source :
- PLoS ONE, Vol 9, Iss 7, p e102495 (2014), PLoS ONE, Lo Sasso, Giuseppe; Ryu, Dongryeol; Mouchiroud, Laurent; Fernando, Samodha C; Anderson, Christopher L; Katsyuba, Elena; Piersigilli, Alessandra; Hottiger, Michael O; Schoonjans, Kristina; Auwerx, Johan (2014). Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer. PLoS ONE, 9(7), e102495. Public Library of Science 10.1371/journal.pone.0102495
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- 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 (Sirt1int / ) 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. © 2014 Lo Sasso et al.
- Subjects :
- endocrine system diseases
Colorectal cancer
Cellular differentiation
lcsh:Medicine
Gut flora
Inflammatory bowel disease
Epithelium
Mice
0302 clinical medicine
Sirtuin 1
Medicine and Health Sciences
lcsh:Science
Mice, Knockout
0303 health sciences
Multidisciplinary
630 Agriculture
biology
Colon Adenocarcinoma
Sodium Dodecyl Sulfate
Cell Differentiation
Colitis
10226 Department of Molecular Mechanisms of Disease
3. Good health
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Goblet Cells
Anatomy
Colorectal Neoplasms
Research Article
Signal Transduction
Paneth Cells
Colon
1100 General Agricultural and Biological Sciences
Gastroenterology and Hepatology
digestive system
Cell Line
03 medical and health sciences
1300 General Biochemistry, Genetics and Molecular Biology
Gastrointestinal Tumors
medicine
Animals
Humans
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Molecular Biology
030304 developmental biology
1000 Multidisciplinary
Neoplastic
Bacteria
Proto-Oncogene Proteins c-ets
Gut Bacteria
Inflammatory Bowel Disease
lcsh:R
Organisms
Biology and Life Sciences
Cancers and Neoplasms
Epithelial Cells
medicine.disease
biology.organism_classification
Small intestine
Gastrointestinal Tract
Biological Tissue
Gene Expression Regulation
Immunology
biology.protein
570 Life sciences
lcsh:Q
Histone deacetylase
Digestive System
Gene Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....60eca567a921d16aa790f9f27eec9dad