title: Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer.
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.
authors.affiliation: Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lo Sasso
authors.affiliation: Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Dongryeol
authors.initials: D
authors.lastname: Ryu
authors.affiliation: Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mouchiroud
authors.affiliation: Department of Animal Science, University of Nebraska, Lincoln, Nebraska, United States of America.
authors.forename: Samodha C
authors.initials: SC
authors.lastname: Fernando
authors.affiliation: Department of Animal Science, University of Nebraska, Lincoln, Nebraska, United States of America; School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, United States of America.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Anderson
authors.affiliation: Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Elena
authors.initials: E
authors.lastname: Katsyuba
authors.affiliation: Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; Institute of Animal Pathology, University of Bern, Bern, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Piersigilli
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
authors.affiliation: Institute of Bioengineering, School of Life Science, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Kristina
authors.initials: K
authors.lastname: Schoonjans
authors.affiliation: Laboratory of Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D020397:Goblet Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D019879:Paneth Cells / Q000378:metabolism* / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000172:deficiency / Q000235:genetics*; D012967:Sodium Dodecyl Sulfate
chemical_list: D029742:Caenorhabditis elegans Proteins; D050783:Proto-Oncogene Proteins c-ets; C519908:Spdef protein, mouse; D012967:Sodium Dodecyl Sulfate; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1