关键词: GDNF/RET ZO-1 enteric glial cells glycyrol ulcerative colitis

Mesh : Animals Glial Cell Line-Derived Neurotrophic Factor / metabolism genetics Colitis, Ulcerative / drug therapy metabolism Mice Humans Zonula Occludens-1 Protein / metabolism genetics Male Neuroglia / drug effects metabolism Intestinal Mucosa / metabolism drug effects Cell Membrane / metabolism drug effects Proto-Oncogene Proteins c-ret / metabolism genetics Mice, Inbred C57BL Coumarins / pharmacology chemistry Signal Transduction / drug effects Glycyrrhiza / chemistry

来  源:   DOI:10.1021/acs.jafc.4c00239

Abstract:
The damage to the mechanical barrier of the intestinal mucosa is the initiating factor and the core link of the progression of ulcerative colitis (UC). Protecting the mechanical barrier of the intestinal mucosa is of great significance for improving the health status of UC patients. ZO-1 is a key scaffold protein of the mechanical barrier of the intestinal mucosa, and its fusion with the membrane of the intestinal epithelium is a necessary condition to maintain the integrity of the mechanical barrier of the intestinal mucosa. Enteric glial cells (EGCs) play an important role in the maintenance of intestinal homeostasis and have become a new target for regulating intestinal health in recent years. In this study, we found that glycyrol (GC), a representative coumarin compound isolated from Licorice (Glycyrrhiza uralensis Fisch, used for medicine and food), can alleviate UC by promoting the production of neurotrophic factor GDNF in mice EGCs. Specifically, we demonstrated that GC promotes the production of GDNF, then activates its receptor RET, promotes ZO-1 fusion with cell membranes, and protects the intestinal mucosal mechanical barrier. The results of this study can provide new ideas for the prevention and treatment of UC.
摘要:
肠粘膜机械屏障的损伤是溃疡性结肠炎(UC)进展的始动因素和核心环节。保护肠黏膜的机械屏障对改善UC患者的健康状况具有重要意义。ZO-1是肠粘膜机械屏障的关键支架蛋白,与肠上皮膜的融合是维持肠粘膜机械屏障完整性的必要条件。肠胶质细胞(EGCs)在维持肠道稳态方面发挥着重要作用,近年来已成为调节肠道健康的新靶点。在这项研究中,我们发现甘醇(GC),一种从甘草中分离出的代表性香豆素化合物(甘草,用于医药和食品),可以通过促进小鼠EGCs中神经营养因子GDNF的产生来缓解UC。具体来说,我们证明了GC促进GDNF的产生,然后激活它的受体RET,促进ZO-1与细胞膜融合,保护肠粘膜机械屏障。本研究结果可为UC的防治提供新思路。
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