Evaluation and inhibition of endoplasmic reticulum stress in the intestinal mucosa of Crohn's disease patients

• Grant number: 20/04407-1
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2021
• End date: January 31, 2023
• Field of knowledge: Biological Sciences - Immunology - Immunogenetics
• Principal Investigator: Raquel Franco Leal
• Grantee: Raquel Franco Leal
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Licio Augusto Velloso ; Marciane Milanski Ferreira ; Maria de Lourdes Setsuko Ayrizono
• Associated research grant(s): 22/09492-2 - 30th United European Gastroenterology Week - UEGWEEK 2022, AR.EXT

Abstract

Inflammatory bowel diseases (IBD) are characterized by chronic intestinal inflammation and represent a relevant health problem with increasing incidence in recent decades in Brazil. Crohn's disease (CD) is one of the two main common form of IBD, which mainly affects young adults where granulomatous transmural inflammation of the mucosa is observed throughout the gastrointestinal tract, but mainly in the terminal ileum and colon. CD is characterized by periods of remission and relapse accompanied by diarrhea, abdominal pain, weight loss, malnutrition, often leading to intestinal lumen stenosis associated with the formation of multiple fistulas. CD is a disease of multifactorial origin that affects genetically susceptible individuals, in which an inadequate immune response results from complex environmental, microbial and innate adaptive immune system interactions. Recent genome wide association (GWAS) and meta-analysis studies have shown that endoplasmic reticulum (ER) stress possibly correlates with the pathogenesis of CD. Thus, the objective of this project will be to investigate the occurrence of ER stress in the intestinal mucosa of CD patients. To do that, intestinal mucosa biopsies from 15 CD patients and 10 non-IBD control patients (CTR) will be subjected to cell culture for evaluation of ER stress and its potential in vitro blockade with chemical chaperone. Modulation of ER stress-related transcripts in intestinal biopsies of CD patients and controls will be evaluated, as well as proteins related to the inflammatory process in the cell culture supernatant. This study may bring major scientific advances contributing to the discovery of the pathophysiological mechanisms of CD, and to identify potential therapeutic targets aimed at healing the intestinal mucosa. (AU)