Regulation of the mucosal epithelial barrier

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-β1, TGF-α, EGF, IL-1β, IFN-γ, 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.