Gastroduodenal mucosal defense

The gastroduodenum has multiple means by which it resists injury from intrinsic and extrinsic factors, including gastric acid, nonsteroidal anti-inflammatory drugs, and Helicobacter pylori. We review recent insights into the mechanisms by which the gastroduodenum resists injury and discuss factors contributing to defensive failure.

Duodenal bicarbonate secretion, a primary defensive mechanism, is mediated by the downregulated in adenoma anion exchanger and is stimulated by estrogens. Nonsteroidal anti-inflammatory drug gastric damage is dependent on toll-like receptor signaling. Portal hypertensive gastropathy impairs extracellular signal-regulated kinase 1/2 phosphorylation, increasing oxidative stress. H. pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses.

Enhanced understanding of the mechanisms of gastroduodenal defense and injury provides new insight into potential therapeutic targets, which contributes towards the development of more well tolerated and more effective therapies.