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.
Highlights
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
There are no indications of genetic mutations related to the mechanism of autophagy associated to UC susceptibility, the transcriptional and protein evaluation of this mechanism in the ileal pouch mucosa is of fundamental relevance
We decided to evaluate apoptosis related genes and there was no statistical differences in BCL2 expression, an anti-apoptotic gene (p > 0.05; Fig. 2G), we found decreased BAX levels in the Familial adenomatous polyposis (FAP) group when compared to CTR group (p < 0.01; Fig. 2F)
Summary
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. Familial adenomatous polyposis (FAP) is an autosomal dominant disease which affects young individuals and is associated with the formation of multiple polyps in the large intestine and rectum, which invariably implies a greater risk of cancer[1,2] Both diseases, despite being different, may require the same surgical procedure. Epigenetic alterations, which have recently been related to the etiology of IBD13,14, can determine transcriptional changes, which in turn help to better understand the mechanisms that predispose patients to the inflammatory process in the ileal pouch justifying its study. We evaluated molecules involved in the autophagy pathways in ileal pouch mucosa of UC and FAP patients, even in the absence of clinical, endoscopic and histological inflammation, in order to understand if there is underlying modulation in these pathways that could mediate molecular inflammation in the IP
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