Article (Scientific journals)
Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homolog in Crohn’s Disease Fibrosis
VIEUJEAN, Sophie; Hu, Shurong; Bequet, Emeline et al.
2021In Journal of Crohn's and Colitis, 15 (10), p. 1737-1750
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Keywords :
CD fibrosis; ER stress; Anterior gradient protein 2 homolog
Abstract :
[en] Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD). It is characterised by an accumulation of fibroblasts differentiating into myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods: We performed a pilot proteomic study comparing the proteome of surface epithelium, isolated by laser-capture microdissection, in normal and fibrotic zones of resected ileal CD strictures (13 zones collected in 5 patients). Proteins of interests were validated by immunohistochemistry (IHC) in ileal and colonic samples of stricturing CD (n=44), pure inflammatory CD (n=29) and control (n=40) subjects. The pro-fibrotic role of one selected epithelial protein was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model. Results: Proteomic study revealed an endoplasmic reticulum (ER) stress proteins increase in the epithelium of CD ileal fibrotic strictures, including Anterior gradient protein 2 homolog (AGR2) and Binding-immunoglobulin protein (BiP). This was confirmed by IHC. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2 intracellular expression and its secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin, led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. By using recombinant protein and blocking agent for AGR2, we demonstrated that the secretion of this protein by epithelial cells can play a role in the myofibroblastic differentiation. Conclusions: The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
VIEUJEAN, Sophie  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de gastroentérologie, hépatologie, onco. digestive
Hu, Shurong
Bequet, Emeline ;  Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
SALEE, Catherine ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Recherche translationnelle en gastroentérologie
MASSOT, Charlotte ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Recherche translationnelle en gastroentérologie
BLETARD, Noëlla ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service d'anatomie et cytologie pathologiques
Pierre, Nicolas  ;  Université de Liège - ULiège > GIGA I3 - Translational gastroenterology
Quesada Calvo, Florence
Baiwir, Dominique  ;  Université de Liège - ULiège > GIGA Platforms
Mazzucchelli, Gabriel  ;  Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
De Pauw, Edwin  ;  Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
COIMBRA MARQUES, Carla ;  Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Chirurgie abdo, sénologique, endocrine et de transplantation
DELVENNE, Philippe ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service d'anatomie et cytologie pathologiques
Rieder, Florian
LOUIS, Edouard  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de gastroentérologie, hépatologie, onco. digestive
MEUWIS, Marie-Alice  ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Recherche translationnelle en gastroentérologie
More authors (6 more) Less
Language :
English
Title :
Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homolog in Crohn’s Disease Fibrosis
Publication date :
October 2021
Journal title :
Journal of Crohn's and Colitis
ISSN :
1873-9946
eISSN :
1876-4479
Publisher :
Elsevier, United Kingdom
Volume :
15
Issue :
10
Pages :
1737-1750
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Epub 02/04/2022.
Available on ORBi :
since 18 April 2021

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