Mansouri Pardis, Mansouri Pegah, Behmard Esmaeil, Najafipour Sohrab, Kouhpayeh Amin, Farjadfar Akbar
Student Research Committee, Fasa University of Medical Sciences, Fasa, Iran; Department of Medical Biotechnology, Fasa University of Medical Sciences, Fasa, Iran.
School of Advanced Technologies in Medicine, Fasa University of Medical Sciences, Fasa, Iran; Zarrin Avaye Kowsar Salamat (ZAX Company), Fasa, Iran.
Int Immunopharmacol. 2025 Jan 10;144:113544. doi: 10.1016/j.intimp.2024.113544. Epub 2024 Nov 20.
Inflammatory bowel disease (IBD) is a chronic condition affecting the gastrointestinal tract, primarily manifesting as ulcerative colitis (UC) or Crohn's disease (CD). Both inflammation and disruption of the intestinal epithelial barrier are key factors in IBD pathogenesis. Substantial evidence has revealed a significant association between aberrant immune responses and impairment of the intestinal epithelial barrier in IBD pathogenesis. The components of the intestinal epithelium, particularly goblet cells and Paneth cells, are crucial to gut homeostasis, as they secrete mucin, antimicrobial peptides (AMPs), and cytokines. Furthermore, impairment of epithelial integrity, which is regulated by tight junctions, is a hallmark of IBD pathology. While common treatments for IBD, such as anti-inflammatory drugs, target various signaling pathways with varying efficacies, therapeutic approaches focused on mucosal and epithelial barrier healing have been largely neglected. Moreover, high costs, side effects, and insufficient or inconsistent therapeutic outcomes remain major drawbacks of conventional anti-IBD drugs. Recent studies on epithelial barrier regeneration and permeability reduction have introduced promising therapeutic targets, including farnesoid X receptor (FXR), urokinase-type plasminogen activator (uPA)-urokinase-type plasminogen activator receptor (uPAR) interaction, fecal microbiota transplantation (FMT), and insulin receptor (INSR). Notably, the simultaneous targeting of intestinal inflammation and promotion of epithelial barrier healing shows promise for efficient IBD treatment. Future research should explore targeted therapies and combination treatments, including natural remedies, microbiota colonization, stem cell approaches, and computer-aided drug design. It is also crucial to focus on accurate prognosis and developing a thorough understanding of IBD development mechanisms.
炎症性肠病（IBD）是一种影响胃肠道的慢性疾病，主要表现为溃疡性结肠炎（UC）或克罗恩病（CD）。炎症和肠道上皮屏障的破坏都是IBD发病机制中的关键因素。大量证据表明，异常免疫反应与IBD发病机制中肠道上皮屏障受损之间存在显著关联。肠道上皮的组成部分，特别是杯状细胞和潘氏细胞，对肠道稳态至关重要，因为它们分泌粘蛋白、抗菌肽（AMPs）和细胞因子。此外，由紧密连接调节的上皮完整性受损是IBD病理学的一个标志。虽然IBD的常见治疗方法，如抗炎药物，以不同的疗效靶向各种信号通路，但专注于黏膜和上皮屏障愈合的治疗方法在很大程度上被忽视了。此外，高成本、副作用以及治疗效果不足或不一致仍然是传统抗IBD药物的主要缺点。最近关于上皮屏障再生和通透性降低的研究引入了有前景的治疗靶点，包括法尼醇X受体（FXR）、尿激酶型纤溶酶原激活剂（uPA）-尿激酶型纤溶酶原激活剂受体（uPAR）相互作用、粪便微生物群移植（FMT）和胰岛素受体（INSR）。值得注意的是，同时靶向肠道炎症和促进上皮屏障愈合显示出有效治疗IBD的前景。未来的研究应探索靶向治疗和联合治疗，包括天然药物、微生物群定植、干细胞方法和计算机辅助药物设计。关注准确的预后并深入了解IBD的发病机制也至关重要。
