دورية أكاديمية
أعرض في EDS

The Glucocorticoid Receptor in Intestinal Epithelial Cells Alleviates Colitis and Associated Colorectal Cancer in Mice.

التفاصيل البيبلوغرافية
العنوان: The Glucocorticoid Receptor in Intestinal Epithelial Cells Alleviates Colitis and Associated Colorectal Cancer in Mice.
المؤلفون: Muzzi C; Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany., Watanabe N; Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany., Twomey E; Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany., Meers GK; Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany., Reichardt HM; Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany., Bohnenberger H; Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany., Reichardt SD; Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Göttingen, Germany. Electronic address: sybille.reichardt@med.uni-goettingen.de.
المصدر: Cellular and molecular gastroenterology and hepatology [Cell Mol Gastroenterol Hepatol] 2021; Vol. 11 (5), pp. 1505-1518. Date of Electronic Publication: 2020 Dec 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Gastroenterological Association Country of Publication: United States NLM ID: 101648302 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-345X (Electronic) Linking ISSN: 2352345X NLM ISO Abbreviation: Cell Mol Gastroenterol Hepatol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Philadelphia, PA : American Gastroenterological Association, [2015]-
مواضيع طبية MeSH: Carcinogenesis/*pathology , Colitis/*complications , Colitis-Associated Neoplasms/*pathology , Inflammation/*pathology , Intestinal Mucosa/*pathology , Receptors, Glucocorticoid/*physiology, Animals ; Azoxymethane/toxicity ; Carcinogenesis/metabolism ; Carcinogens/toxicity ; Colitis/chemically induced ; Colitis/pathology ; Colitis-Associated Neoplasms/etiology ; Colitis-Associated Neoplasms/metabolism ; Dextran Sulfate/toxicity ; Female ; Gene Expression Profiling ; Inflammation/etiology ; Inflammation/metabolism ; Intestinal Mucosa/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Permeability ; Receptors, Glucocorticoid/deficiency
مستخلص: Background & Aims: Inflammatory bowel disease is commonly treated by administration of glucocorticoids. While the importance of intestinal epithelial cells for the pathogenesis of this disorder is widely accepted, their role as target cells for glucocorticoids has not been explored. To address this issue, we induced colonic inflammation in GR villin mice, which carry an inducible deletion of the glucocorticoid receptor in intestinal epithelial cells.
Methods: Colitis and colitis-associated colorectal cancer were induced by administration of dextran sulfate sodium and azoxymethane in mice. Clinical parameters, epithelial permeability and tumor development were monitored during disease progression. Colon tissue, lamina propria cells and intestinal epithelial cells were examined by gene expression analyses, flow cytometry, histopathology, and immunohistochemistry.
Results: The absence of the intestinal epithelial glucocorticoid receptor aggravated clinical symptoms and tissue damage, and compromised epithelial barrier integrity during colitis. Gene expression of chemokines, pattern recognition receptors and molecules controlling epithelial permeability was dysregulated in intestinal epithelial cells of GR villin mice, leading to a reduced recruitment and a hyperactivation of leukocytes in the lamina propria of the colon. Importantly, the exaggerated inflammatory response in GR villin mice also enhanced associated tumorigenesis, resulting in a higher number and larger size of tumors in the colon.
Conclusions: Our results reveal an important role of intestinal epithelial cells as targets of glucocorticoid action in inflammatory bowel disease and suggest that the efficacy with which colitis is kept at bay directly affects the progression of colorectal cancer.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
التعليقات: Comment in: Cell Mol Gastroenterol Hepatol. 2021;11(5):1541-1542. (PMID: 33684386)
فهرسة مساهمة: Keywords: Colon; Epithelial Barrier; Inflammation; Tumor
المشرفين على المادة: 0 (Carcinogens)
0 (Receptors, Glucocorticoid)
9042-14-2 (Dextran Sulfate)
MO0N1J0SEN (Azoxymethane)
تواريخ الأحداث: Date Created: 20201214 Date Completed: 20220308 Latest Revision: 20220308
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8039723
DOI: 10.1016/j.jcmgh.2020.12.006
PMID: 33316454
قاعدة البيانات: MEDLINE
الوصف
تدمد:2352-345X
DOI:10.1016/j.jcmgh.2020.12.006