{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T23:29:57Z","timestamp":1782170997216,"version":"3.54.5"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T00:00:00Z","timestamp":1581033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR000058"],"award-info":[{"award-number":["UL1TR000058"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009993","name":"Center for Clinical and Translational Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009993","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011684","name":"Crohn's and Colitis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK49691"],"award-info":[{"award-number":["DK49691"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Endoplasmic reticulum (ER) stress is an essential response of epithelial and immune cells to inflammation in Crohn\u2019s 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\u2019s disease have not been examined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Subepithelial myofibroblasts were isolated from the affected ileum and normal ileum of patients with each Montreal phenotype of Crohn\u2019s disease and from normal ileum in non-Crohn\u2019s subjects. Binding of GRP78 to latent TGF-\u03b21 and its subcellular trafficking was examined using proximity ligation-hybridization assay (PLA). The effects of XBP1 and ATF6 on TGF-\u03b21 expression were measured using DNA-ChIP and luciferase reporter assay. Endoplasmic reticulum stress components, TGF-\u03b21, 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In SEMF of strictured ileum from patients with B2 Crohn\u2019s disease, expression of ER stress sensors increased significantly. Tunicamycin elicited time-dependent increase in GRP78 protein levels, direct interaction with latent TGF-\u03b21, and activated TGF-\u03b21 signaling. The TGFB1 DNA-binding activity of ATF-6\u03b1 and XBP1 were significantly increased and elicited increased TGFB1 transcription in SEMF-isolated from affected ileum. The levels of ER stress components, TGF-\u03b21, and collagen expression in SEMF were significantly decreased following knockdown of DNMT1 or GRP78 by 5-Azacytidine treatment or overexpression of miR-199a-5p.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Endoplasmic reticulum stress is present in SEMF of patients susceptible to fibrostenotic Crohn\u2019s 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\u2019s disease.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izaa015","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T13:13:47Z","timestamp":1581081227000},"page":"809-819","source":"Crossref","is-referenced-by-count":36,"title":["Endoplasmic Reticulum Stress in Subepithelial Myofibroblasts Increases the TGF-\u03b21 Activity That Regulates Fibrosis in Crohn\u2019s Disease"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-9764","authenticated-orcid":false,"given":"Chao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA"},{"name":"Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Grider","sequence":"first","affiliation":[{"name":"VCU Program for Enteric Neurosciences, Virginia Commonwealth University, Richmond, VA, USA"},{"name":"Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA"},{"name":"Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karnam S","family":"Murthy","sequence":"first","affiliation":[{"name":"VCU Program for Enteric Neurosciences, Virginia Commonwealth University, Richmond, VA, USA"},{"name":"Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, VA, USA"},{"name":"Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA, 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