Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homologue in Crohn’s Disease Fibrosis
| العنوان: | Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homologue in Crohn’s Disease Fibrosis |
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| المؤلفون: | Florence Quesada Calvo, Florian Rieder, Dominique Baiwir, Marie-Alice Meuwis, Charlotte Massot, Noëlla Bletard, Edwin De Pauw, Philippe Delvenne, Shurong Hu, Nicolas Pierre, Sophie Vieujean, Emeline Bequet, Edouard Louis, Carla Coimbra Marques, Gabriel Mazzucchelli, Catherine Salee |
| المصدر: | J Crohns Colitis |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Proteomics, 0301 basic medicine, Colon, AGR2, Pilot Projects, Cell Line, 03 medical and health sciences, HT29 Cells, Mucoproteins, 0302 clinical medicine, Crohn Disease, Ileum, Humans, Medicine, Intestinal Mucosa, Fibroblast, Anterior Gradient Protein 2 Homolog, Oncogene Proteins, business.industry, Endoplasmic reticulum, Gastroenterology, Original Articles, General Medicine, Endoplasmic Reticulum Stress, Fibrosis, Molecular biology, Intestinal epithelium, Epithelium, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Unfolded protein response, business |
| الوصف: | 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 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. Results Proteomic 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. Conclusions The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2. |
| تدمد: | 1876-4479 1873-9946 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f77398c49809431fca3237c3f4bc17f8Test https://doi.org/10.1093/ecco-jcc/jjab061Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f77398c49809431fca3237c3f4bc17f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18764479 18739946 |
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