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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.

SUBMITTER: Lo Sasso G

PROVIDER: S-EPMC4094521 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Lo Sasso Giuseppe G Ryu Dongryeol D Mouchiroud Laurent L Fernando Samodha C SC Anderson Christopher L CL Katsyuba Elena E Piersigilli Alessandra A Hottiger Michael O MO Schoonjans Kristina K Auwerx Johan J

PloS one 20140711 7

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 ...[more]

PMID: 25013930

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