Agradecimentos: This work was supported by Consejería de Innovación, Ciencia y Empresa-Junta de Andalucía (P09-AGR-5185, Polfanat). We thank “Centro de Investigación, Tecnología e Innovación (CITIUS)” of the University of Seville for providing technical assistance

Interleukin-10-deficient (IL-10 (−/−)) mice spontaneously develop chronic colitis and adenocarcinoma through the dysplasia sequence. Autophagy malfunction is associated to inflammatory bowel disease (IBD) and colorectal cancer (CRC) pathogenesis. Autophagy is regulated by silent information...

Interleukin-10-deficient (IL-10 (−/−)) mice spontaneously develop chronic colitis and adenocarcinoma through the dysplasia sequence. Autophagy malfunction is associated to inflammatory bowel disease (IBD) and colorectal cancer (CRC) pathogenesis. Autophagy is regulated by silent information regulator-1 (SIRT1), a NAD +-dependent histone deacetylase. Our aim was to investigate the expression changes of SIRT1-AMPK-autophagy pathway in the progression from chronic colitis to CRC. We studied C57BL/6-IL-10-deficient mice between 6 and 18 weeks of age. Macroscopic and histological analysis, and characterization of inflammatory and tumor biomarkers were performed. IL-10-deficient mice developed colitis from the age of 6 weeks onward. The severity of inflammation and dysplasia, and the proliferative activity increased gradually with age. IL-10 (−/−) mice were characterized by improved levels of TNF-α and decreased expression of SIRT1. Moreover, our findings show an increase in p-AMPK expression and an activation of the autophagy in IL-10 (−/−) mice from all stages, evidenced by the accumulation of LC3-II protein, the increase in Beclin 1 expression and the reduction in Bcl-2 levels.
SIRT1-AMPK-autophagy pathway may be involved in the maintenance of chronic inflammation and dysplasia development in the IL-10-deficient mice model. Modulation of this pathway could be a novel strategy for IBD and CRC treatment

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