Molecular mechanisms of pancreatic stone formation in chronic pancreatitis

Shigeru B.H. Ko, Sakiko Azuma, Toshiyuki Yoshikawa, Akiko Yamamoto, Kazuhiro Kyokane, Minoru S.H. Ko, Hiroshi Ishiguro

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


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 HCO3- 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.

Original languageEnglish
Article numberArticle 415
JournalFrontiers in Physiology
Volume3 NOV
Publication statusPublished - 2012
Externally publishedYes


  • Bicarbonate secretion
  • CFTR
  • Chronic pancreatitis
  • Cytoplasmic mislocalization
  • Pancreatic stone formation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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