Göke M, Podolsky D K
Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Baillieres Clin Gastroenterol. 1996 Sep;10(3):393-405. doi: 10.1016/s0950-3528(96)90049-4.
Rapid re-sealing of the intestinal epithelial barrier is initially accomplished by migration of viable epithelial cells from the wound edge into the denuded area ('restitution') and only later by cell proliferation. Whereas proliferation of intestinal epithelial cells has been studied intensively, much less is known about the pivotal initial phase of cell migration. Restitution appears to be modulated by peptide growth factors/cytokines, extracellular matrix molecules, and luminally secreted products of mucus-producing cells (schematically summarized in Figure 1). Recent work has demonstrated that various cytokines (TGF-beta 1, TGF-alpha, EGF, IL-1 beta, IFN-gamma, basic FGF, KGF and HGF) present in the intestinal mucosa enhance intestinal epithelial restitution, presumably by mediating its effects through the basolateral pole of the epithelial monolayer. In addition to their effects on cell adhesion, differentiation, and spatial organization, the extracellular matrix molecules on which intestinal epithelial cells reside also have the potential to stimulate intestinal epithelial cell migration. The basement membrane components fibronectin and collagen type IV may be especially important. Finally, trefoil factors, a recently identified family of peptides which are secreted onto the luminal surface where they form the visco-elastic mucus layer through interaction with mucin glycoproteins, also promote the important process of restitution through a pathway distinct from that used by factors acting at the basolateral cell surface.
肠道上皮屏障的快速重新封闭最初是通过存活的上皮细胞从伤口边缘迁移到剥脱区域来实现的（“修复”），而细胞增殖则是在这之后才发生。虽然对肠道上皮细胞的增殖进行了深入研究，但对于细胞迁移的关键初始阶段却知之甚少。修复似乎受到肽生长因子/细胞因子、细胞外基质分子以及黏液分泌细胞向管腔分泌的产物的调节（如图1示意性总结）。最近的研究表明，存在于肠黏膜中的多种细胞因子（转化生长因子β1、转化生长因子α、表皮生长因子、白细胞介素1β、干扰素γ、碱性成纤维细胞生长因子、角质形成细胞生长因子和肝细胞生长因子）可增强肠道上皮修复，推测是通过上皮单层的基底外侧极介导其作用。除了对细胞黏附、分化和空间组织的影响外，肠道上皮细胞所附着的细胞外基质分子也有可能刺激肠道上皮细胞迁移。基底膜成分纤连蛋白和IV型胶原可能尤为重要。最后，三叶因子是最近发现的一类肽，它们分泌到管腔表面，通过与黏蛋白糖蛋白相互作用形成黏弹性黏液层，也通过一条不同于作用于基底外侧细胞表面的因子所使用的途径促进重要的修复过程。
