Journal of Crohn's & colitis · 2025
The angiotensin receptor blocker, losartan, reduces inflammation and fibrosis, and prevents relapse of fibrosis after steroid-induced remission, in mice prone to Crohn's disease-like ileitis.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Artone Serena, Ray Shuvra, Williams Joseph J, Akbulut Kenan, Cordero Paul, Gómez-Úriz Ana M, Friedman Hannah R, Saline Anna V, Hart Isabel M, Vadivelan Elakia, Parigi Tommaso L, Pietropaoli Davide, Latella Giovanni, Sanderson Jeremy D, De Salvo Carlo, Oben Jude A, Pizarro Theresa T, De Santis Stefania
Аннотация
BACKGROUND AND AIMS: The renin-angiotensin system (RAS) is known to modulate fibrosis, which is a common complication of ileal Crohn's disease. We tested the efficacy of losartan, an angiotensin receptor blocker, to treat intestinal fibrosis in relevant preclinical models of Crohn's-like disease.
METHODS: Effector molecules of the RAS were mined in a large publicly available RNA-Seq dataset of intestinal biopsies from Crohn's patients and healthy individuals, and the presence of associated proteins was confirmed by immunohistochemistry in full-thickness intestinal tissues. Losartan's 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's-like disease that progressively develops both ileal-specific inflammation and fibrosis, using either therapeutic or maintenance of remission (treatment after dexamethasone) approaches.
RESULTS: 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's 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.
CONCLUSIONS: 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's patients.
METHODS: Effector molecules of the RAS were mined in a large publicly available RNA-Seq dataset of intestinal biopsies from Crohn's patients and healthy individuals, and the presence of associated proteins was confirmed by immunohistochemistry in full-thickness intestinal tissues. Losartan's 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's-like disease that progressively develops both ileal-specific inflammation and fibrosis, using either therapeutic or maintenance of remission (treatment after dexamethasone) approaches.
RESULTS: 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's 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.
CONCLUSIONS: 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's patients.