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

钙蛋白酶是Ca^<2+>依赖性的细胞溶质蛋白酶，其对于各种细胞过程是不可缺少的。在这里，我们表明，两个胃肠道特异性钙蛋白酶8和9的基因突变的小鼠容易受到应激诱导的胃损伤。此外，这些钙蛋白酶形成稳定的复合物，其中两种分子都是活性所必需的。胃粘膜的完整性取决于一个复杂的防御系统，该系统在面对各种刺激物时发挥作用，包括酒精、非甾体抗炎药（NSAID）和幽门螺杆菌。持续或不适当地摄入这些刺激物往往会导致严重的胃病。因此，我们的研究结果可能有助于开发新的治疗策略，人类胃病引起的刺激物。

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.