{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:37:59Z","timestamp":1783579079480,"version":"3.55.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK125293"],"award-info":[{"award-number":["R01 DK125293"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 AI141350"],"award-info":[{"award-number":["P01 AI141350"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK097948"],"award-info":[{"award-number":["P30 DK097948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK097948"],"award-info":[{"award-number":["P30 DK097948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011684","name":"Crohn\u2019s & Colitis Foundation","doi-asserted-by":"crossref","award":["RFA 326877"],"award-info":[{"award-number":["RFA 326877"]}],"id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R25 CA221718"],"award-info":[{"award-number":["R25 CA221718"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>The renin-angiotensin system (RAS) is known to modulate fibrosis, which is a common complication of ileal Crohn\u2019s disease. We tested the efficacy of losartan, an angiotensin receptor blocker, to treat intestinal fibrosis in relevant preclinical models of Crohn\u2019s-like disease.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Effector molecules of the RAS were mined in a large publicly available RNA-Seq dataset of intestinal biopsies from Crohn\u2019s patients and healthy individuals, and the presence of associated proteins was confirmed by immunohistochemistry in full-thickness intestinal tissues. Losartan\u2019s efficacy in altering mediators of the RAS and of fibrosis was tested in vitro using activated CCD-18Co fibroblasts, while its in vivo effects were investigated by administering losartan to SAMP1\/YitFc (SAMP) mice, a well-described model of Crohn\u2019s-like disease that progressively develops both ileal-specific inflammation and fibrosis, using either therapeutic or maintenance of remission (treatment after dexamethasone) approaches.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Angiotensinogen, an upstream regulator of the RAS, and the downstream effector, angiotensin II receptor type 1, expressed on target cells, are both increased in involved vs non-involved gut mucosa from Crohn\u2019s patients compared to healthy controls. In vitro, losartan suppresses the expression of molecules related to fibrosis, fibroblast-to-myofibroblast differentiation, collagen deposition, and cytoskeletal alterations. In vivo, losartan decreases both inflammation and fibrosis in SAMP mice with established disease, and prevents the reoccurrence of fibrosis following a novel relapse protocol.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Losartan, and other drugs targeting the RAS, may serve as an effective treatment to successfully dampen intestinal fibrosis during active inflammation, as well as prevent its progression after corticosteroid-induced remission in Crohn\u2019s patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf083","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T10:43:33Z","timestamp":1747737813000},"source":"Crossref","is-referenced-by-count":8,"title":["The angiotensin receptor blocker, losartan, reduces inflammation and fibrosis, and prevents relapse of fibrosis after steroid-induced remission, in mice prone to Crohn\u2019s disease-like ileitis"],"prefix":"10.1093","volume":"19","author":[{"given":"Serena","family":"Artone","sequence":"first","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]},{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila , L\u2019Aquila ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuvra","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]},{"name":"IBD Centre, Department of Gastroenterology, Guy\u2019s and St Thomas\u2019 Hospitals NHS Trust , London, England ,","place":["United Kingdom"]},{"name":"Institute for Liver & Digestive Health, University College London , England,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph J","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenan","family":"Akbulut","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cordero","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]},{"name":"Institute for Liver & Digestive Health, University College London , England,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M","family":"G\u00f3mez-\u00dariz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah R","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]},{"name":"Department of Microbiology & Immunology, University of North Carolina , Chapel Hill, NC ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna V","family":"Saline","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel M","family":"Hart","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elakia","family":"Vadivelan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso L","family":"Parigi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]},{"name":"IBD Unit, Department of Gastroenterology, IRCCS Ospedale San Raffaele , Milan ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Pietropaoli","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila , L\u2019Aquila ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6341-5711","authenticated-orcid":false,"given":"Giovanni","family":"Latella","sequence":"additional","affiliation":[{"name":"Department of Life, Health & Environmental Sciences, University of L\u2019Aquila , L\u2019Aquila ,","place":["Italy"]},{"name":"Unit of Gastroenterology, Hepatology, and Nutrition, San Salvatore Hospital , L\u2019Aquila ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy D","family":"Sanderson","sequence":"additional","affiliation":[{"name":"IBD Centre, Department of Gastroenterology, Guy\u2019s and St Thomas\u2019 Hospitals NHS Trust , London, England ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"De Salvo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude A","family":"Oben","sequence":"additional","affiliation":[{"name":"IBD Centre, Department of Gastroenterology, Guy\u2019s and St Thomas\u2019 Hospitals NHS Trust , London, England ,","place":["United Kingdom"]},{"name":"Institute for Liver & Digestive Health, University College London , England,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa T","family":"Pizarro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"De Santis","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine , Cleveland, OH 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