Gut homeostasis, injury, and healing: New therapeutic targets

Figure 1 Normal gastrointestinal homeostasis, injury, and healing. A: Structure of gastric epithelium in healthy, injured, and repaired states. A healthy gastric barrier is essential to maintain gastric homeostasis. In a healthy state, there is an equilibrium between gastric injury and mucosal healing. An excess of destructive factors such as acid, pepsin, nonsteroidal anti-inflammatory drugs (NSAIDs), and H. pylori leads to gastric barrier disruption. These noxious agents then diffuse deeper into the mucosa and create wounds. Epithelial cells at the edge of the injury redifferentiate to a migratory phenotype and collectively migrate as a sheet to close the wound. After successful restitution, the migrated cells redifferentiate to more specialized phenotypes. B: A diagram depicting the structure and cell types of gastric epithelium. C: In the injured state, epithelial cells at the edge of the wound spread and redifferentiate to a migratory phenotype, losing their classical apical brush border and assuming a more squamous morphology. Then, they migrate as a sheet to cover the injured area, with cells at the front of the migrating sheet transmitting traction forces to cells farther back via cell-cell contacts. Epithelial cells behind these migrating cells subsequently proliferate to provide more cells to fully cover larger wounds. D: Cells that have migrated across the defect may themselves then proliferate once the barrier has been reformed. In addition, following migration and proliferation, the migrated cells redifferentiate back to more specialized phenotypes. E: Structure of small intestinal epithelium in healthy and injured states. F: Structure of large intestinal epithelium in healthy and injured states. A healthy intestinal barrier is essential to maintain intestinal homeostasis. In the healthy state, there is an equilibrium between intestinal injury and mucosal healing. An excess of destructive factors such as NSAIDs, inflammation, bile acid, and toxic luminal substances leads to intestinal barrier disruption. These noxious agents then diffuse deeper into the mucosa and create wounds. Epithelial cells at the edge of the injury follow the processes described in the figure legends for in Figure 1C and D. IESC: Intestinal epithelial stem cells; EEC: Enteroendocrine cells; GC: Goblet cells; NSAIDs: Nonsteroidal anti-inflammatory drugs; H. pylori: Helicobacter pylori; PG: Prostaglandins; ECL cells: Enterochromaffin-like cells; PC: Paneth cells; IESC: Intestinal epithelial stem cells.