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Endoplasmic reticulum stress and unfolded protein response are involved in paediatric inflammatory bowel disease

Anna Negroni1, Enrica Prete1, Roberta Vitali1

  • 1Department of Radiobiology and Human Health, ENEA, Rome, Italy.

Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
|June 24, 2014
PubMed

Insights

Endoplasmic reticulum stress and unfolded protein response pathways are implicated in pediatric inflammatory bowel disease. Gene expression analysis revealed significant upregulation in inflamed tissues, correlating with inflammation markers.

Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Immunology

Background:

  • Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are linked to adult inflammatory bowel disease (IBD).
  • The role of these pathways in pediatric IBD remains less understood.
  • This study investigates ER stress and UPR involvement in pediatric IBD.

Purpose of the Study:

  • To assess the expression of key ER stress and UPR genes in pediatric IBD patients.
  • To correlate gene expression with the degree of intestinal inflammation.
  • To elucidate the role of ER stress and UPR in the pathogenesis of pediatric IBD.

Main Methods:

  • Analysis of ER stress marker HSPA5 and UPR genes (IRE-XBP1, PERK-ATF4, ATF6) via real-time PCR and Western blot.
  • Biopsies from 28 pediatric IBD patients (inflamed and uninflamed) and 10 controls were analyzed.
  • Correlation analysis with interleukin-8 (IL-8) levels as an inflammation marker.

Main Results:

  • Significant upregulation of HSPA5, PDIA4, and XBP1 mRNA in inflamed pediatric IBD colonic mucosa compared to controls.
  • Increased HSPA5, PDIA4, ATF6, and phospho-IRE proteins indicated activation of IRE-XBP1 and ATF6 UPR pathways.
  • Positive correlation found between IL-8 levels and upregulated genes in inflamed mucosa.

Conclusions:

  • Deregulation of ER stress and UPR genes is a significant factor in pediatric IBD pathogenesis.
  • These pathways are actively involved in the inflammatory response of pediatric IBD.
  • Targeting ER stress and UPR pathways may offer therapeutic potential for pediatric IBD.
Abstract

Keywords:
Crohn's diseaseGene expressionIntestinal inflammationUlcerative colitis

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