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Type: Artigo
Title: Expression Patterns Of Sirtuin 1-ampk-autophagy Pathway In Chronic Colitis And Inflammation-associated Colon Neoplasia In Il-10-deficient Mice
Author: Talero
Elena; Alcaide
Antonio; Avila-Roman
Javier; Garcia-Maurino
Sofia; Vendramini-Costa
Debora; Motilva
Abstract: 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. Methods: 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. Results: 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-alpha 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. Conclusions: 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. (C) 2016 Elsevier B.V. All rights reserved.
Subject: Chronic Inflammation
Colon Carcinogenesis
Il-10-deficient Mice
Editor: Elsevier Science BV
Citation: International Immunopharmacology. Elsevier Science Bv, v. 35, p. 248 - 256, 2016.
Rights: fechado
Identifier DOI: 10.1016/j.intimp.2016.03.046
Date Issue: 2016
Appears in Collections:Unicamp - Artigos e Outros Documentos

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