Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis
Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis
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DOI：
10.1172/jci9411
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发表时间：
2000-09-01
影响因子：
15.9
通讯作者：
Deussing, J
中科院分区：
文献类型：
--
作者：
Halangk, W;Lerch, MM;Deussing, J
胰腺自身过早激活的消化蛋白酶的自身消化被认为是急性胰腺炎发病的一个重要事件。胰腺内消化酶原激活的机制尚不清楚，但最近的一项假设预测，溶酶体组织蛋白酶B （CTSB）重新分布到含有酶原的亚细胞区室触发了这一事件。为了验证这一假设，我们使用了ctsb缺陷小鼠，其中ctsb基因通过靶向破坏被删除。实验促分泌剂诱导胰腺炎后，ctsb（-/-）动物胰腺胰蛋白酶活性比ctsb（+/+）动物低80%以上。血清淀粉酶和脂肪酶活性或腺泡组织坏死程度显示，ctsb（-/-）小鼠胰腺损伤降低50%。这些实验为我们所知的组织蛋白酶B在胰腺内胰蛋白酶原激活和急性胰腺炎发病中发挥作用提供了第一个确凿的证据。
Autodigestion of the pancreas by its own prematurely activated digestive proteases is thought to be an important event in the onset of acute pancreatitis. The mechanism responsible for the intrapancreatic activation of digestive zymogens is unknown, but a recent hypothesis predicts that a redistribution of lysosomal cathepsin B (CTSB) into a zymogen-containing subcellular compartment triggers this event. To test this hypothesis, we used CTSB-deficient mice in which the ctsb gene had been deleted by targeted disruption. After induction of experimental secretagogue-induced pancreatitis, the trypsin activity in the pancreas of ctsb(-/-) animals was more than 80% lower than in ctsb(+/+) animals. Pancreatic damage as indicated by serum activities of amylase and lipase, or by the extent of acinar tissue necrosis, was 50% lower in ctsb(-/-) animals. These experiments provide the first conclusive evidence to our knowledge that cathepsin B plays a role in intrapancreatic trypsinogen activation and the onset of acute pancreatitis.