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3. Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer

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, and University of Zurich

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
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.

Published
2014

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