Molecular mechanisms of pancreatic stone formation in chronic pancreatitis.
Molecular mechanisms of pancreatic stone formation in chronic pancreatitis.
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DOI：
10.3389/fphys.2012.00415
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发表时间：
2012
影响因子：
4
通讯作者：
Ishiguro H
中科院分区：
文献类型：
--
作者：
Ko SB;Azuma S;Yoshikawa T;Yamamoto A;Kyokane K;Ko MS;Ishiguro H
慢性胰腺炎(CP)是一种胰腺分泌实质被破坏并被纤维化取代的进行性炎症性疾病。胰腺导管内结石(S)的存在对CP的诊断很重要；然而，CP胰腺结石形成的确切分子机制仍很不清楚。囊性纤维化跨膜电导调节因子(CFTR)是一种表达于胰管细胞顶端质膜的氯离子通道，在胰管细胞的分泌中起中心作用。在以前的研究中，我们已经发现CFTR在所有类型的CP中都错误地定位于胰管细胞的胞浆中，而皮质类固醇使CFTR的定位正常化到适当的顶膜，至少在自身免疫性胰腺炎中是这样。从这些观察中，我们可以得出结论，CFTR的错误定位是CP中蛋白质塞形成的原因之一，从而导致胰腺结石的形成。考虑到我们观察到CFTR的错误定位也发生在酒精性或特发性CP中，很可能这些病理情况也可以用皮质类固醇治疗，从而防止这些患者的胰腺结石形成。肯定需要进一步的研究来澄清这些基本问题。
Chronic pancreatitis (CP) is a progressive inflammatory disease in which the pancreatic secretory parenchyma is destroyed and replaced by fibrosis. The presence of intraductal pancreatic stone(s) is important for the diagnosis of CP; however, the precise molecular mechanisms of pancreatic stone formation in CP were left largely unknown. Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel expressed in the apical plasma membrane of pancreatic duct cells and plays a central role in secretion. In previous studies, we have found that CFTR is largely mislocalized to the cytoplasm of pancreatic duct cells in all forms of CP and corticosteroids normalizes the localization of CFTR to the proper apical membrane at least in autoimmune pancreatitis. From these observations, we could conclude that the mislocalization of CFTR is a cause of protein plug formation in CP, subsequently resulting in pancreatic stone formation. Considering our observation that the mislocalization of CFTR also occurs in alcoholic or idiopathic CP, it is very likely that these pathological conditions can also be treated by corticosteroids, thereby preventing pancreatic stone formation in these patients. Further studies are definitely required to clarify these fundamental issues.
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影响因子：
3.6
作者：
Frulloni, Luca;Scattolini, Chiara;Vantini, Italo
通讯作者：
Vantini, Italo
影响因子：
3.6
作者：
Furuya, S;Naruse, S;Hayakawa, T
通讯作者：
Hayakawa, T
皮质类固醇在自身免疫性胰腺炎中纠正管道中的异常CFTR定位和再生腺泡细胞。
影响因子：
29.4
作者：
Ko SB;Mizuno N;Yatabe Y;Yoshikawa T;Ishiguro H;Yamamoto A;Azuma S;Naruse S;Yamao K;Muallem S;Goto H
通讯作者：
Goto H
DOI：
10.1016/j.bbrc.2011.06.093
发表时间：
2011-07-15
影响因子：
3.1
作者：
Ko, Shigeru B. H.;Yamamoto, Akiko;Goto, Hidemi
通讯作者：
Goto, Hidemi
影响因子：
5.5
作者：
Song, Ying;Yamamoto, Akiko;Ishiguro, Hiroshi
通讯作者：
Ishiguro, Hiroshi