PXD022214

PXD022214 is an original dataset announced via ProteomeXchange.

Title	Fibrosis associated changes detected in the proteome of surface epithelium overlying Crohn’s Disease Strictures
Description	Background and aims: Intestinal fibrosis is a common complication of Crohn’s disease (CD). It is characterised by an excessive accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined. Methods: A total of 113 CD and control subjects were studied. 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 (n=5). Selected proteins were validated by immunohistochemistry (IHC) in colonic and ileal samples of stricturing CD patients (n=44), pure inflammatory CD (n=29) and control subjects (n=40). Functional assays with cell lines cultures and a fibroblast to myofibroblast differentiation model were used to assess the role of the highlighted epithelial proteins in CD fibrosis. Results: Proteomic study revealed an endoplasmic reticulum (ER) stress and unfolded protein response (UPR) markers increase in the epithelium overlying ileal fibrotic strictures, involving Anterior gradient protein 2 homolog (AGR2) and Binding immunoglobulin protein (BiP). This was confirmed by IHC. The ER stress induction in intestinal epithelial cells increased AGR2 as well as BiP expression and led to an extracellular secreted AGR2. A fibroblast to myofibroblast differentiation was obtained with the supernatant of intestinal epithelial cells pre-conditioned by ER stress and with recombinant AGR2. Conclusions: AGR2 and other ER stress markers are increased within the intestinal epithelium overlying fibrotic strictures and might contribute to profibrotic signals involved in CD fibrosis.
HostingRepository	PRIDE
AnnounceDate	2022-05-27
AnnouncementXML	Submission_2022-05-27_05:23:07.551.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marie-Alice Meuwis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-28 01:29:33	ID requested
⏵ 1	2022-05-27 05:23:08	announced

Vieujean S, Hu S, Bequet E, Salee C, Massot C, Bletard N, Pierre N, Quesada Calvo F, Baiwir D, Mazzucchelli G, De Pauw E, Coimbra Marques C, Delvenne P, Rieder F, Louis E, Meuwis MA, Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homologue in Crohn's Disease Fibrosis. J Crohns Colitis, 15(10):1737-1750(2021) [pubmed]

submitter keyword: Inflammatory bowel disease, ileum, fibrostenosis, surface epithelium, label free proteomics

Edouard LOUIS
contact affiliation	Translational gastroenterology, GIGA institute, University of Liege ULiege Belgium and Hepatogastro entreology and digestive oncology University hospitalof Liège, CHU Liège
contact email	Edouard.Louis@Uliege.be
lab head
Marie-Alice Meuwis
contact affiliation	translational gastroenterology laboratory University of Liege, GIGA institute: university hospital CHU Liège, BE
contact email	marie-alice.meuwis@uliege.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022214
     1. Label: PRIDE project
     2. Name: Fibrosis associated changes detected in the proteome of surface epithelium overlying Crohn’s Disease Strictures