Department of Pharmacology, School of Medicine, Kanazawa Medical University, Uchinada 920-0293, Japan.
Division of Genomic Science and Microbiology, School of Medicine, University of Fukui, Eiheiji 910-1193, Japan.
Int J Mol Sci. 2023 Mar 30;24(7):6508. doi: 10.3390/ijms24076508.
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is an intestinal disorder that causes prolonged inflammation of the gastrointestinal tract. Currently, the etiology of IBD is not fully understood and treatments are insufficient to completely cure the disease. In addition to absorbing essential nutrients, intestinal epithelial cells prevent the entry of foreign antigens (micro-organisms and undigested food) through mucus secretion and epithelial barrier formation. Disruption of the intestinal epithelial homeostasis exacerbates inflammation. Thus, the maintenance and reinforcement of epithelial function may have therapeutic benefits in the treatment of IBD. Muscarinic acetylcholine receptors (mAChRs) are G protein-coupled receptors for acetylcholine that are expressed in intestinal epithelial cells. Recent studies have revealed the role of mAChRs in the maintenance of intestinal epithelial homeostasis. The importance of non-neuronal acetylcholine in mAChR activation in epithelial cells has also been recognized. This review aimed to summarize recent advances in research on mAChRs for intestinal epithelial homeostasis and the involvement of non-neuronal acetylcholine systems, and highlight their potential as targets for IBD therapy.
炎症性肠病(IBD)包括克罗恩病和溃疡性结肠炎,是一种肠道疾病,会导致胃肠道长时间发炎。目前,IBD 的病因尚未完全阐明,治疗方法也不足以完全治愈该疾病。除了吸收必需的营养物质外,肠道上皮细胞还通过分泌黏液和形成上皮屏障来防止外来抗原(微生物和未消化的食物)进入。肠道上皮细胞稳态的破坏会加剧炎症。因此,维持和增强上皮功能可能对 IBD 的治疗具有治疗益处。毒蕈碱型乙酰胆碱受体(mAChR)是肠道上皮细胞中乙酰胆碱的 G 蛋白偶联受体。最近的研究揭示了 mAChR 在维持肠道上皮细胞稳态中的作用。非神经元乙酰胆碱在 mAChR 激活中的重要性也已得到认可。本综述旨在总结 mAChR 对肠道上皮细胞稳态的最新研究进展以及非神经元乙酰胆碱系统的参与,并强调它们作为 IBD 治疗靶点的潜力。