Secreted and membrane-bound mucins and idiopathic peptic ulcer disease.

The incidence of Helicobacter pylori and non-steroidal anti-inflammatory drug (NSAID)-negative peptic ulcer disease has increased over the last two decades, especially in the Western world and in countries with low H. pylori infection rates. Idiopathic peptic ulcer disease is a recently described entity which relates to peptic ulcers not caused by H. pylori, NSAID/aspirin therapy, other ulcerogenic organisms and drugs, or other rare malignant and benign diseases. Structural and secreted mucins create the unstirred gastric mucus layer and maintain a stable pH above the gastric mucosa. This mucous layer prevents enzymatic attack by acid and pepsin. Inhibition of cyclooxygenase by NSAID and aspirin inhibits prostaglandin production, inhibits mucin and bicarbonate secretion, and exposes the mucosa to the toxic effects of acid and intragastric enzymes. There is also a complex relationship between H. pylori and different mucin subtypes which on one hand facilitates mucin invasion but on the other hand protects the gastric mucosa. Genetic and epigenetic changes in the mucin molecule may be responsible for idiopathic peptic ulcer disease, but this hypothesis must be further investigated. Herein, the mucin hypothesis of idiopathic peptic ulcer disease is explored.