Sturm Andreas, Dignass Axel U
Medizinische Klinik I, Markus-Krankenhaus, Wilhelm-Epstein-Strasse 2, 60431 Frankfurt/Main, Germany.
World J Gastroenterol. 2008 Jan 21;14(3):348-53. doi: 10.3748/wjg.14.348.
Inflammatory bowel disease is characterized by a chronic inflammation of the intestinal mucosa. The mucosal epithelium of the alimentary tract constitutes a key element of the mucosal barrier to a broad spectrum of deleterious substances present within the intestinal lumen including bacterial microorganisms, various dietary factors, gastrointestinal secretory products and drugs. In addition, this mucosal barrier can be disturbed in the course of various intestinal disorders including inflammatory bowel diseases. Fortunately, the integrity of the gastrointestinal surface epithelium is rapidly reestablished even after extensive destruction. Rapid resealing of the epithelial barrier following injuries is accomplished by a process termed epithelial restitution, followed by more delayed mechanisms of epithelial wound healing including increased epithelial cell proliferation and epithelial cell differentiation. Restitution of the intestinal surface epithelium is modulated by a range of highly divergent factors among them a broad spectrum of structurally distinct regulatory peptides, variously described as growth factors or cytokines. Several regulatory peptide factors act from the basolateral site of the epithelial surface and enhance epithelial cell restitution through TGF-beta-dependent pathways. In contrast, members of the trefoil factor family (TFF peptides) appear to stimulate epithelial restitution in conjunction with mucin glycoproteins through a TGF-beta-independent mechanism from the apical site of the intestinal epithelium. In addition, a number of other peptide molecules like extracellular matrix factors and blood clotting factors and also non-peptide molecules including phospholipids, short-chain fatty acids (SCFA), adenine nucleotides, trace elements and pharmacological agents modulate intestinal epithelial repair mechanisms. Repeated damage and injury of the intestinal surface are key features of various intestinal disorders including inflammatory bowel diseases and require constant repair of the epithelium. Enhancement of intestinal repair mechanisms by regulatory peptides or other modulatory factors may provide future approaches for the treatment of diseases that are characterized by injuries of the epithelial surface.
炎症性肠病的特征是肠道黏膜的慢性炎症。消化道的黏膜上皮构成了黏膜屏障的关键要素，可抵御肠腔内存在的多种有害物质，包括细菌微生物、各种饮食因素、胃肠分泌产物及药物。此外，在包括炎症性肠病在内的各种肠道疾病过程中，这种黏膜屏障可能会受到干扰。幸运的是，即使在广泛破坏后，胃肠道表面上皮的完整性也能迅速重建。损伤后上皮屏障的快速重新封闭是通过一个称为上皮修复的过程完成的，随后是更延迟的上皮伤口愈合机制，包括上皮细胞增殖增加和上皮细胞分化。肠道表面上皮的修复受到一系列高度不同的因素调节，其中包括多种结构不同的调节肽，这些调节肽被不同地描述为生长因子或细胞因子。几种调节肽因子从上皮表面的基底外侧发挥作用，并通过转化生长因子-β（TGF-β）依赖的途径增强上皮细胞修复。相比之下，三叶因子家族成员（TFF肽）似乎通过一种不依赖TGF-β的机制，从肠道上皮的顶端与黏蛋白糖蛋白一起刺激上皮修复。此外，许多其他肽分子，如细胞外基质因子和凝血因子，以及非肽分子，包括磷脂、短链脂肪酸（SCFA）、腺嘌呤核苷酸、微量元素和药物制剂，都能调节肠道上皮修复机制。肠道表面的反复损伤是包括炎症性肠病在内的各种肠道疾病的关键特征，需要不断修复上皮。通过调节肽或其他调节因子增强肠道修复机制可能为治疗以上皮表面损伤为特征的疾病提供未来的方法。
