The roles of mislocalization of membrane proteins in the development of chronic pancreatitis

慢性胰腺炎是一种进行性胰腺疾病。越来越多的证据表明，表达于胰管细胞顶端质膜的CFTR通道是胰腺炎的致病因素之一。然而，目前尚不清楚CFTR功能障碍是如何导致胰腺炎的。在慢性胰腺炎中，CFTR主要错误定位于胰管细胞的胞浆中。当RNA干扰使豚鼠胰管细胞CFTR表达下调时，胰液分泌量显著减少至对照组的50%左右。这些结果表明，CFTR的表达直接调节胰管细胞的液体分泌，因此CFTR功能障碍是慢性胰腺炎发生的机制之一。

Chronic pancreatitis is a progressive disease of the pancreas. Accumulating evidence suggests that CFTR channel, which is expressed in the apical plasma membrane of pancreatic duct cells, is one of the factors that cause pancreatitis. However, it remains unknown how CFTR dysfunction cause pancreatitis. In chronic pancreatitis, CFTR is largely mislocalized in the cytoplasm of pancreatic duct cells. When CFTR expression was reduced by RNA interference in isolated guinea-pig pancreatic duct cells, pancreatic fluid secretion was remarkably reduce to ～50% of control. These findings indicate that CFTR expression directly regulates the fluid secretion from pancreatic duct cells and therefore CFTR dysfunction is one of the mechanisms to develop chronic pancreatitis.