Distribution of epithelial endoplasmic reticulum stress-related proteins in adult and pediatric Crohn's disease: Association with inflammation and fibrosis. - 2025
Distribution of epithelial endoplasmic reticulum stress-related proteins in adult and pediatric Crohn's disease: Association with inflammation and fibrosis.
Bequet, Emeline; Salée, Catherine; Bletard, Net al.
2025 • In Digestive and Liver Disease, 57 (6), p. 1197-1208
[en] BACKGROUND/AIMS: Intestinal strictures in Crohn's disease (CD), driven by fibrosis remain challenging to treat. Current treatments focus on inflammation, but are less effective against fibrosis. Endoplasmic Reticulum Stress-Related Proteins, including Protein disulfide isomerases (PDIs), may contribute to fibrosis; their roles in CD remain unclear. This study investigated the distribution of AGR2, BiP, PDIA6, ERP44 in intestinal epithelium and their association with fibrosis and inflammation in pediatric and adult CD. METHODS: We retrospectively analyzed 224 patients (2009-2023). CD patients with and without strictures, non IBD controls, and ulcerative colitis patients were compared. Immunohistochemistry assessed Endoplasmic Reticulum Stress-Related protein distribution in epithelium. H&E and Masson's trichrome staining evaluated inflammation and fibrosis. Correlations between protein distribution, inflammation and fibrosis were examined. RESULTS: AGR2 and BiP were increased in fibro-inflammatory and fibrotic intestinal epithelial tissues, especially in pediatric-onset CD. ERP44 was associated with fibrosis exclusively in pediatric CD. PDIA6 was upregulated in CD compared to non IBD, without fibrosis association. Distinct protein distribution patterns were observed between pediatric and adult CD, and between ileum and colon. CONCLUSIONS: Distinct patterns of AGR2, BiP, PDIA6, and ERP44 in fibrotic and inflammatory intestinal tissues suggest potential roles in CD-associated fibrosis, warranting exploration as biomarkers or therapeutic targets.
Disciplines :
Gastroenterology & hepatology Pediatrics
Author, co-author :
Bequet, Emeline ; Université de Liège - ULiège > Département des sciences cliniques > Médecine générale
Salée, Catherine ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Bletard, N; Department of Pathology, University Hospital Liège, Belgium.
Massot, Charlotte ; Université de Liège - ULiège > GIGA > GIGA Immunobiology - Translational gastroenterology
Fonzé, F; Laboratory of Translational Gastroenterology, GIGA-Institute, University of Liège, Liège, Belgium.
Sarter, H; Public Health, Epidemiology and Economic Health, EPIMAD Registry, Regional house of clinical research, F-59000 Lille University and Hospital, Lille, France.
Ley, D; Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France, Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, CHU Lille, F-59000 Lille, France.
Colinet, S; Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, CHC MontLégia, Liège, Belgium.
Delvenne, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Louis, Edouard ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Vieujean, Sophie ✱; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
✱ These authors have contributed equally to this work.
Language :
English
Title :
Distribution of epithelial endoplasmic reticulum stress-related proteins in adult and pediatric Crohn's disease: Association with inflammation and fibrosis.
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