ArticleInflammatory bowel diseases2020
Endoplasmic Reticulum Stress in Subepithelial Myofibroblasts Increases the TGF-β1 Activity That Regulates Fibrosis in Crohn's Disease.
Article in Inflammatory bowel diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Dynamic Organelle Remodeling in HIV-Associated Myocardial Disease: Mechanisms, Fibrotic Pathways, and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
- Article
- Hyperactivation of ATF4/TGF-β1 signaling contributes to the progressive cardiac fibrosis in Arrhythmogenic cardiomyopathy caused by DSG2 Variant.BMC medicine · 2024Article
- Preventing fibrosis in IBD: update on immune pathways and clinical strategies.Expert review of clinical immunology · 2024Review
- Inflammation accelerating intestinal fibrosis: from mechanism to clinic.European journal of medical research · 2024Review
- Anti-fibrotics in inflammatory bowel diseases: Challenges and successes.Advances in pharmacology (San Diego, Calif.) · 2024Review
- Genomic insights into pediatric intestinal inflammatory and eosinophilic disorders using single-cell RNA-sequencing.Frontiers in immunology · 2024Article
- Anti-fibrotic effect of ciglitazone in HRV-induced airway remodelling cell model.Journal of cellular and molecular medicine · 2023Article
- Dendritic cells: the yin and yang in disease progression.Frontiers in immunology · 2023Review
- Immunological Regulation of Intestinal Fibrosis in Inflammatory Bowel Disease.Inflammatory bowel diseases · 2022Review
- Co-expression of fibrotic genes in inflammatory bowel disease; A localized event?Frontiers in immunology · 2022Article
- Endoplasmic Reticulum Stress of Gut Enterocyte and Intestinal Diseases.Frontiers in molecular biosciences · 2022Review
- Potential Role of Epithelial Endoplasmic Reticulum Stress and Anterior Gradient Protein 2 Homologue in Crohn's Disease Fibrosis.Journal of Crohn's & colitis · 2021Article
- Novel mechanisms and clinical trial endpoints in intestinal fibrosis.Immunological reviews · 2021Review
- Endoplasmic reticulum stress and autophagy are involved in adipocyte-induced fibrosis in hepatic stellate cells.Molecular and cellular biochemistry · 2021Article
- Development of a Human Intestinal Organoid Model forStem cells international · 2021Article
- Unraveling the Molecular Nexus between GPCRs, ERS, and EMT.Mediators of inflammation · 2021Review
- Mechanism of fibrosis and stricture formation in Crohn's disease.Scandinavian journal of immunology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundEndoplasmic 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.
methodsSubepithelial 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.
resultsIn 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.
conclusionsEndoplasmic 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.
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