Regulation of intestinal regeneration: new insights

Intestinal regeneration is the process by which intestinal injury penetrating deep to the lamina propria heals. The regenerative process involves epithelial cell migration and proliferation, changes in cellular function, adaptation of subepithelial tissues, and contraction of the injured area. This requires interaction of multiple cell types. While many observations have been made about the process of regeneration, its regulation is not well understood. Previous studies, performed primarily in a serosal patch model, have identified many potential regulatory factors. These include location and size of the injury, other associated injury, e.g., resection, and a variety of agents that influence one or more of the primary processes involved. Epidermal growth factor (EGF), in particular, appears to play a role in many aspects of regeneration. Recent advances in the understanding of intestinal growth regulation have provided new insights into the regulation of intestinal regeneration. Developmental studies in genetically manipulated mice suggest a role for gene products not previously implicated in regeneration. The importance of apoptosis in growth regulation has recently been emphasized. Mesenchymal-epithelial interactions have gained greater appreciation. Finally, it has become clear that immune cells and cytokines are important factors in this process. Transforming growth factor-beta (TGFbeta) has been implicated as another important regulator of several of the processes involved in intestinal regulation. Improved understanding of the regulation of intestinal regeneration will lead to new therapeutic approaches to stimulate intestinal healing in the clinical setting.