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Loss of Sirt1 Function Improves Intestinal Anti-Bacterial Defense and Protects from Colitis-Induced Colorectal Cancer

2014; Public Library of Science; Volume: 9; Issue: 7 Linguagem: Inglês

10.1371/journal.pone.0102495

1932-6203

Giuseppe Lo Sasso, Dongryeol Ryu, Laurent Mouchiroud, Samodha C. Fernando, Christopher L. Anderson, Elena Katsyuba, Alessandra Piersigilli, Michael O. Hottiger, Kristina Schoonjans, Johan Auwerx,

Ginseng Biological Effects and Applications

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.