Clinical and translational medicine · 2025
Liraglutide upregulates the Cftr gene and regulates the mucus transcriptome profile in Brunner's glands in mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание 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.
Voetmann Louise Marie, Rolin Bidda, Kirk Rikke Kaae, Knudsen Lotte Bjerre, Merkestein Myrte, Ahnfelt-Rønne Jonas, Kodal Anne Louise, Jessen Carsten, Ozen Asli, Pyke Charles, Hansen Axel Kornerup
Аннотация
BACKGROUND: The metabolic syndrome encompasses a state of inflammation and metabolic dysfunction, possibly mediated via a disturbed intestinal barrier. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as liraglutide, have shown promising anti-inflammatory effects beyond glucose lowering and weight loss, but the underlying mechanism remains to be elucidated. We hypothesised that GLP-1RAs improve the intestinal barrier function and overall inflammatory status by direct gene activation in mucus-secreting Brunner's glands in the mouse duodenum, known for their high density of glucagon-like peptide-1 receptors (GLP-1Rs).
METHODS: Using bulk RNA sequencing, in situ hybridisation, and immunohistochemistry, we analysed the change in the genetic phenotype of mouse Brunner's gland cells following GLP-1R activation by liraglutide.
RESULTS: We show that liraglutide induces a novel and robust upregulation of the gene for the Cystic fibrosis transmembrane conductance regulator, Cftr, in Brunner's glands as a part of an overall genetic phenotype involved in ion channel activity, mucus secretion, and hydration via GLP-1R activation. Additionally, we found a robust upregulation of the genes Muc5b, Il33, Ren1, and Vldlr in Brunner's glands.
CONCLUSION: Collectively, our results imply an enhanced mucus response from Brunner's glands following GLP-1R activation, which might play a role in the effect of GLP-1.
METHODS: Using bulk RNA sequencing, in situ hybridisation, and immunohistochemistry, we analysed the change in the genetic phenotype of mouse Brunner's gland cells following GLP-1R activation by liraglutide.
RESULTS: We show that liraglutide induces a novel and robust upregulation of the gene for the Cystic fibrosis transmembrane conductance regulator, Cftr, in Brunner's glands as a part of an overall genetic phenotype involved in ion channel activity, mucus secretion, and hydration via GLP-1R activation. Additionally, we found a robust upregulation of the genes Muc5b, Il33, Ren1, and Vldlr in Brunner's glands.
CONCLUSION: Collectively, our results imply an enhanced mucus response from Brunner's glands following GLP-1R activation, which might play a role in the effect of GLP-1.