Transcriptional analysis of intestinal mucosa and mesenteric adipose tissue of patients with Crohn's disease

Abstract

Crohn's disease (CD) is a chronic intestinal disorder with a multifactorial etiology, whose incidence has increased during the last three decades. Intestinal involvement is transmural, thus there is possibility of developing fistulas and strictures. The role of mesenteric adipose tissue (MAT) in the development of these complications, as well as, with the disease etiology is not well established. The characteristic macroscopic increase of intestinal MAT near the affected intestinal area, with circumferential involvement of the intestinal loop was noticed since the description of CD, but there are few studies that address this issue. In this study, we intend to evaluate samples of intestinal mucosa and MAT of patients with ileocecal CD, and from control subjects, which were already collected. Transcriptional study will be conducted using RNA-seq analysis, and the genes of interest will be validated in an independent cohort by RT-PCR, immunoblotting and histological study. We will focus mainly on transcripts related to the occurrence of endoplasmic reticulum stress in both the intestinal mucosa and MAT. To achieve this goal, RNA-seq analysis will be performed for samples of 10 patients with ileocecal CD, whose samples of intestinal mucosa (ICD Group) and of MAT were already obtained (ACD); 10 patients without inflammatory bowel disease (control group AC); 10 subjects with normal colonoscopy (control group IC). The validation cohort will comprise over 10 other individuals for each group mentioned above. Thus, this study may identify tissue-specific differences that could be involved in susceptibility to disease, and also may identify potential biomarkers and targets of pharmacological agents, individualizing therapies. (AU)