Analysis of gastric mucosal defense mechanisms involving gastrointestinal tract-specific calpains

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Calpains are Ca^<2+->dependent cytosolic proteases that are indispensable for various cellular processes. Here we show that mice with mutations in the genes for two gastrointestinal tract-specific calpains 8 and 9 are susceptible to stress-induced gastric injury. Moreover, these calpains form a stable complex, in which both molecules are essential for activity. Gastric mucosal integrity depends on a complex defense system that acts in the face of a variety of irritants, including alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs), and Helicobacter pylori. The continuous or improper ingestion of these irritants often leads to serious gastropathies. Our results might therefore contribute to the development of new therapeutic strategies for human gastropathies induced by irritants.