title: Expression patterns of sirtuin 1-AMPK-autophagy pathway in chronic colitis and inflammation-associated colon neoplasia in IL-10-deficient mice.
abstract: BACKGROUND
  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 18weeks 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 6weeks 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.
  
  
  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.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Spain. Electronic address: etalero@us.es.
authors.forename: Elena
authors.initials: E
authors.lastname: Talero
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Alcaide
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Ávila-Román
authors.affiliation: Department of Plant Biology and Ecology, Faculty of Biology, University of Seville, Spain.
authors.forename: Sofía
authors.initials: S
authors.lastname: García-Mauriño
authors.affiliation: Organic Chemistry Department, Chemistry Institute, UNICAMP, Campinas, SP, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Vendramini-Costa
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Motilva
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000235:genetics; D063646:Carcinogenesis; D002908:Chronic Disease; D003092:Colitis / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000378:metabolism / Q000473:pathology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D016753:Interleukin-10 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D016753:Interleukin-10; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: Autophagy; Chronic inflammation; Colon carcinogenesis; IL-10-deficient mice; SIRT1