ArticleJournal of Crohn's & colitis2021
Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homologue in Crohn's Disease Fibrosis.
Article in Journal of Crohn's & colitis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Pharmacogenomic Pathways Underlying Variable Vedolizumab Response in Crohn's Disease Patients: A Rare-Variant Analysis.Biomedicines · 2026Article
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
- Microbial metabolic memory in inflammatory bowel disease: microbiota-derived metabolites, host-microbe reprogramming, and relapse susceptibility.Frontiers in microbiology · 2026Review
- Interpretable Machine Learning Identifies Hub Biomarkers of Renal Fibrosis and Their Potential Medical Applications.Drug design, development and therapy · 2026Article
- Article
- Adiponectin deficiency prevents chronic colitis-associated colonic fibrosis via inhibiting CXCL13 production.Journal of advanced research · 2025Article
- Integrating Proteomics into Personalized Medicine for Inflammatory Bowel Disease-Reality or Challenge?International journal of molecular sciences · 2025Review
- Intestinal fibrosis associated with inflammatory bowel disease: Known and unknown.Chinese medical journal · 2025Review
- Essential roles of the unfolded protein response in intestinal physiology.eGastroenterology · 2024Review
- PEPerMINT: peptide abundance imputation in mass spectrometry-based proteomics using graph neural networks.Bioinformatics (Oxford, England) · 2024Article
- Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024Review
- Natural compound fraxinellone ameliorates intestinal fibrosis in mice via direct intervention of HSP47-collagen interaction in the epithelium.Acta pharmacologica Sinica · 2023Article
- Potential Role of AGR2 for Mammalian Skin Wound Healing.International journal of molecular sciences · 2023Review
- Endoplasmic reticulum stress related genome-wide Mendelian randomization identifies therapeutic genes for ulcerative colitis and Crohn's disease.Frontiers in genetics · 2023Article
- Comprehensive analysis of endoplasmic reticulum stress-associated genes signature of ulcerative colitis.Frontiers in immunology · 2023Article
- Multi-omics in Crohn's disease: New insights from inside.Computational and structural biotechnology journal · 2023Review
- Article
- Hypoxia-inducible factor as a bridge between healthy barrier function, wound healing, and fibrosis.American journal of physiology. Cell physiology · 2022Review
- Intestinal strictures in Crohn's disease: a 2021 update.Therapeutic advances in gastroenterology · 2022Review
- Co-expression of fibrotic genes in inflammatory bowel disease; A localized event?Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND AND
aimsIntestinal 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.
methodsWe 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 five 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.
resultsProteomic study revealed an endoplasmic reticulum [ER] stress proteins increase in the epithelium of CD ileal fibrotic strictures, including anterior gradient protein 2 homologue [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.
conclusionsThe development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2.
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