上皮钙敏感受体缺乏会改变肠道完整性并促进促炎免疫反应。
Epithelial CaSR deficiency alters intestinal integrity and promotes proinflammatory immune responses.
作者信息
Cheng Sam X, Lightfoot Yaíma L, Yang Tao, Zadeh Mojgan, Tang Lieqi, Sahay Bikash, Wang Gary P, Owen Jennifer L, Mohamadzadeh Mansour
机构信息
Division of Gastroenterology, Department of Pediatrics, University of Florida, Gainesville, FL 32607, USA.
Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32608, USA; Division of Gastroenterology, Hepatology & Nutrition, Department of Medicine, University of Florida, Gainesville, FL 32610, USA.
出版信息
FEBS Lett. 2014 Nov 17;588(22):4158-66. doi: 10.1016/j.febslet.2014.05.007. Epub 2014 May 17.
Abstract
The intestinal epithelium is equipped with sensing receptor mechanisms that interact with luminal microorganisms and nutrients to regulate barrier function and gut immune responses, thereby maintaining intestinal homeostasis. Herein, we clarify the role of the extracellular calcium-sensing receptor (CaSR) using intestinal epithelium-specific Casr(-/-) mice. Epithelial CaSR deficiency diminished intestinal barrier function, altered microbiota composition, and skewed immune responses towards proinflammatory. Consequently, Casr(-/-) mice were significantly more prone to chemically induced intestinal inflammation resulting in colitis. Accordingly, CaSR represents a potential therapeutic target for autoinflammatory disorders, including inflammatory bowel diseases.
摘要
肠道上皮配备有传感受体机制，可与管腔微生物和营养物质相互作用，以调节屏障功能和肠道免疫反应，从而维持肠道内环境稳定。在此，我们利用肠道上皮特异性Casr(-/-)小鼠阐明细胞外钙敏感受体（CaSR）的作用。上皮CaSR缺乏会削弱肠道屏障功能，改变微生物群组成，并使免疫反应向促炎方向倾斜。因此，Casr(-/-)小鼠明显更容易受到化学诱导的肠道炎症影响，从而导致结肠炎。相应地，CaSR代表了包括炎症性肠病在内的自身炎症性疾病的潜在治疗靶点。
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