scholarly journals Fusobacterium nucleatum Activates Endoplasmic Reticulum Stress to Promote Crohn’s Disease Development via the Upregulation of CARD3 Expression

2020 ◽  
Vol 11 ◽  
Author(s):  
Pan Cao ◽  
Yongyu Chen ◽  
Yan Chen ◽  
Wenhao Su ◽  
Na Zhan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Endoplasmic Reticulum Stress ◽  
Fusobacterium Nucleatum ◽  
Disease Development

scholarly journals Endoplasmic Reticulum Stress in Subepithelial Myofibroblasts Increases the TGF-β1 Activity That Regulates Fibrosis in Crohn’s Disease

2020 ◽  
Vol 26 (6) ◽  
pp. 809-819 ◽  
Author(s):  
Chao Li ◽  
John R Grider ◽  
Karnam S Murthy ◽  
Jaime Bohl ◽  
Emily Rivet ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Endoplasmic Reticulum Stress ◽  
Er Stress ◽  
Direct Interaction ◽  
Binding Activity ◽  
Luciferase Reporter ◽  
Stress Components ◽  
Tgf Β1

Abstract Background Endoplasmic reticulum (ER) stress is an essential response of epithelial and immune cells to inflammation in Crohn’s disease. The presence and mechanisms that might regulate the ER stress response in subepithelial myofibroblasts (SEMFs) and its role in the development of fibrosis in patients with Crohn’s disease have not been examined. Methods Subepithelial myofibroblasts were isolated from the affected ileum and normal ileum of patients with each Montreal phenotype of Crohn’s disease and from normal ileum in non-Crohn’s subjects. Binding of GRP78 to latent TGF-β1 and its subcellular trafficking was examined using proximity ligation-hybridization assay (PLA). The effects of XBP1 and ATF6 on TGF-β1 expression were measured using DNA-ChIP and luciferase reporter assay. Endoplasmic reticulum stress components, TGF-β1, and collagen levels were analyzed in SEMF transfected with siRNA-mediated knockdown of DNMT1 and GRP78 or with DNMT1 inhibitor 5-Azacytidine or with overexpression of miR-199a-5p. Results In SEMF of strictured ileum from patients with B2 Crohn’s disease, expression of ER stress sensors increased significantly. Tunicamycin elicited time-dependent increase in GRP78 protein levels, direct interaction with latent TGF-β1, and activated TGF-β1 signaling. The TGFB1 DNA-binding activity of ATF-6α and XBP1 were significantly increased and elicited increased TGFB1 transcription in SEMF-isolated from affected ileum. The levels of ER stress components, TGF-β1, and collagen expression in SEMF were significantly decreased following knockdown of DNMT1 or GRP78 by 5-Azacytidine treatment or overexpression of miR-199a-5p. Conclusions Endoplasmic reticulum stress is present in SEMF of patients susceptible to fibrostenotic Crohn’s disease and can contribute to development of fibrosis. Targeting ER stress may represent a novel therapeutic target to prevent fibrosis in patients with fibrostenotic Crohn’s disease.

scholarly journals DOP080 Endoplasmic reticulum stress in bordering epithelium of Crohn’s disease patients with intestinal fibrosis

2018 ◽  
Vol 12 (supplement_1) ◽  
pp. S084-S084
Author(s):  
S Hu ◽  
N Bletard ◽  
C Massot ◽  
N Pierre ◽  
F Quesada Calvo ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Endoplasmic Reticulum Stress ◽  
Intestinal Fibrosis
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