GASTROINTESTINAL EPITHELIAL RESPONSE TO INJURY

Repair of superficial damage to gastrointestinal mucosa occurs by a pr ocess called restitution. In restitution, epithelial cells near the wo und rapidly flatten, extend lamellipodia, and migrate to reform an int act epithelial barrier. The signaling pathways responsible for control ling these processes are poorly understood. Multiple lines of evidence suggest the direct involvement of the mitogen-activated protein (MAP) kinase signaling pathways in restitution, Cytokines that augment epit helial wound repair generally have in common the ability to activate t he MAP kinase pathway involving Pas and extracellular signal-regulated kinase (ERK). Pas function is necessary for efficient migration follo wing wounding. Tissue injury results in the rapid expression of immedi ate response genes including c-Fos and c-Jun. Activation of the MAP ki nase pathways of ERK and c-Jun amino-terminal protein kinase is known to directly activate these immediate response genes and thus provides a potential mechanism for transcriptional regulation of other genes ne cessary for restitution and wound repair.