P013 Potential Role of Epithelial Protein Disulphide Isomerases in Crohn’s Disease Fibrosis
| العنوان: | P013 Potential Role of Epithelial Protein Disulphide Isomerases in Crohn’s Disease Fibrosis |
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| المؤلفون: | Nicolas Pierre, L Edouard, Marie-Alice Meuwis, Shurong Hu, Dominique Baiwir, E. De Pauw, Philippe Delvenne, C Coimbra Marques, Sophie Vieujean, Noëlla Bletard, F Quesada Calvo, Charlotte Massot, Emeline Bequet, Gabriel Mazzucchelli, Catherine Salee |
| المصدر: | Journal of Crohn's and Colitis. 15:S134-S135 |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Crohn's disease, business.industry, Gastroenterology, General Medicine, Isomerase, medicine.disease, Intestinal epithelium, Extracellular matrix, Paracrine signalling, Fibrosis, Heat shock protein, medicine, Cancer research, Protein disulfide-isomerase, business |
| الوصف: | Background Intestinal fibrosis is a common complication of Crohn’s disease (CD) characterized by an accumulation of fibroblasts differentiating into activated myofibroblasts secreting excessive extracellular matrix. In in-vitro experiments, this myofibroblastic differentiation is elicited by a whole series of factors among which transforming growth factor-β1 (TGF-β1) seems to play a key role. 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). The pro-fibrotic role of selected epithelial proteins 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), Protein disulphide isomerase A6 (PDIA6) and Endoplasmic reticulum resident protein 44 (ERP44) which are 3 protein disulphide isomerases. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2, PDIA6, ERP44 as well as TGF-β1 intracellular expression and their secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin (Tm), led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. The application of blocking agents for AGR2, PDIA6, ERP44 or TGF-β1 in the supernatant of these Tm-pre-conditioned HT-29 cells, attenuated the myofibroblastic differentiation induced by this supernatant, suggesting a pro-fibrotic role of these secreted epithelial proteins. Conclusion The development of CD fibrotic strictures may involve ER stress in epithelial cells, releasing a whole set of proteins into their environment, including AGR2, PDIA6, ERP44 as well as TGF-β1, which could exercise a pro-fibrotic role through a paracrine action. |
| تدمد: | 1876-4479 1873-9946 |
| DOI: | 10.1093/ecco-jcc/jjab076.142 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::2e11c5aa37decf492a95f67587764b94 https://doi.org/10.1093/ecco-jcc/jjab076.142 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........2e11c5aa37decf492a95f67587764b94 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18764479 18739946 |
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| DOI: | 10.1093/ecco-jcc/jjab076.142 |