Autophagy in ileal pouch mucosa of patients with ulcerative colitis and familial polyposis adenomatous

• Grant number: 16/15231-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2016
• End date: October 31, 2017
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Raquel Franco Leal
• Grantee: Leandro Minatel Vidal de Negreiros
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Restorative retocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for ulcerative colitis (UC), which is refractory to clinical therapy and for familial adenomatous polyposis (FAP) with many rectal polyps. A common complication after this procedure in UC patients is pouchitis, being rare in FAP. Previous studies showed an increase of pro-inflammatory cytokines and apoptosis in ileal pouch mucosa of patients with UC when compared with FAP and controls. However, there are no studies evaluating the cell autophagy, which is associated with the apoptosis pathway. For this purpose, we will evaluate the autophagy mechanism in ileal pouch and in the afferent loop mucosa of UC and FAP patients submitted to IPAA compared to normal distal ileum controls. Sixteen patients with J pouch will be studied. Also, eight patients with normal ileum colonoscopy will be the control group. The expression of Atg16L1, MAP1LC3A, Beclin-1, Atg5, Ulk-1, TNF-±, IL-10, and their encoded proteins will be analyzed. Biopsies will be obtained for immunoblot and for real time PCR. The absence of pouchitis will be determined by clinical, endoscopic and histological parameters, according to Pouchitis Disease Activity Index (PDAI). The study was approved by the Ethics Committee of University of Campinas. Nonparametric tests will be performed for statistical analysis. The level of significance will be p<0,05. Those transcriptional and protein modulation may contribute to a better understanding of the factors that predispose to pouchitis as well as identify potential biomarkers of this process.