Summary

Many genes, some encoding peptides, are upregulated after mucosal damage in the gastrointestinal mucosa: we have looked for an ordered sequence in the expression of genes such as c-fos, c-jun,egr-1, Sp-1, epidermal growth factor, transforming growth factors α and β, trefoil peptides, epidermal growth factor receptor, hepatocyte growth factor, c-met, fibroblast growth factor, platelet derived growth factor, and vascular endothelial growth factor. All of these gene products play an important reparative role, assisting appropriate healing of the damaged mucosa. There does indeed seem to be a temporal sequence in this gene expression, but there is a certain degree of redundancy within the system, both in terms of receptor binding and the function of the gene products. However, it is probable that the integrated function of these genes and their products safeguard the important healing properties of the gastrointestinal mucosa. Although the function of individual gene products is of course important, it now seems critical to explore the inter-relations between these genes and their encoded products to explain fully mucosal regeneration after damage.

The gastrointestinal tract is subjected to a wide variety of mucosal challenges. Helicobacter pyloriassociated ulcer disease, non-steroidal anti-inflammatory drug (NSAID) associated ulcers, alcohol induced mucosal injury, and a variety of inflammatory conditions, including ulcerative colitis and Crohn's disease. No matter what the cause of the ulceration, the mucosa usually responds rapidly by triggering off a cascade of repair mechanisms to stimulate repair and restore mucosal integrity. Many genes are induced by the damage: apart from early response genes such as c-fos, c-jun,egr-1, and Sp-1, genes encoding peptides are particularly well represented; there is increasing evidence that at least 30 such genes are involved in the process. In the main, most investigators have …