Ileal pouch of ulcerative colitis and familial adenomatous polyposis patients exhibit modulation of autophagy markers

Sci Rep. 2018 Feb 8;8(1):2619. doi: 10.1038/s41598-018-20938-5.

Abstract

Total retocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment. Pouchitis is one of the most common complications after this procedure. Defects in autophagy have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum. Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal IP were evaluated. The control group consisted of eight patients with normal colonoscopy. There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group. There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group. Although the LC3II levels by immunoblot were higher in the UC group, LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group. Corroborating these results, there was an increase of p62 by immunoblot in the UC group. These findings indicated a modulation of macroautophagy markers in the IP, which may explain the mucosa inflammation predisposition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / metabolism*
  • Adult
  • Aged
  • Autophagy*
  • Autophagy-Related Protein 5 / metabolism
  • Biomarkers / metabolism
  • Colitis, Ulcerative / metabolism*
  • Colonic Pouches / pathology
  • Female
  • Humans
  • Intestinal Mucosa / metabolism*
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Pouchitis / metabolism*
  • Proctocolectomy, Restorative / adverse effects
  • Proctocolectomy, Restorative / methods
  • RNA-Binding Proteins / metabolism

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • Biomarkers
  • MAP1LC3A protein, human
  • MAP1LC3B protein, human
  • Microtubule-Associated Proteins
  • P62 protein, human
  • RNA-Binding Proteins