Molecular mechanisms of pancreatic stone formation in chronic pancreatitis

Shigeru Ko, Sakiko Azuma, Toshiyuki Yoshikawa, Akiko Yamamoto, Kazuhiro Kyokane, Minoru Ko, Hiroshi Ishiguro

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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
DOIs
Publication statusPublished - 2012

Fingerprint

Chronic Pancreatitis
Cystic Fibrosis Transmembrane Conductance Regulator
Pancreatic Ducts
Adrenal Cortex Hormones
Chloride Channels
Pancreatitis
Cytoplasm
Fibrosis
Cell Membrane
Membranes
Proteins

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Ko, S., Azuma, S., Yoshikawa, T., Yamamoto, A., Kyokane, K., Ko, M., & Ishiguro, H. (2012). Molecular mechanisms of pancreatic stone formation in chronic pancreatitis. Frontiers in Physiology, 3 NOV, [Article 415]. https://doi.org/10.3389/fphys.2012.00415

Molecular mechanisms of pancreatic stone formation in chronic pancreatitis. / Ko, Shigeru; Azuma, Sakiko; Yoshikawa, Toshiyuki; Yamamoto, Akiko; Kyokane, Kazuhiro; Ko, Minoru; Ishiguro, Hiroshi.

In: Frontiers in Physiology, Vol. 3 NOV, Article 415, 2012.

Research output: Contribution to journalArticle

Ko, S, Azuma, S, Yoshikawa, T, Yamamoto, A, Kyokane, K, Ko, M & Ishiguro, H 2012, 'Molecular mechanisms of pancreatic stone formation in chronic pancreatitis', Frontiers in Physiology, vol. 3 NOV, Article 415. https://doi.org/10.3389/fphys.2012.00415
Ko, Shigeru ; Azuma, Sakiko ; Yoshikawa, Toshiyuki ; Yamamoto, Akiko ; Kyokane, Kazuhiro ; Ko, Minoru ; Ishiguro, Hiroshi. / Molecular mechanisms of pancreatic stone formation in chronic pancreatitis. In: Frontiers in Physiology. 2012 ; Vol. 3 NOV.
@article{2dec42a335e14067b849409af4320d8d,
title = "Molecular mechanisms of pancreatic stone formation in chronic pancreatitis",
abstract = "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.",
keywords = "Bicarbonate secretion, CFTR, Chronic pancreatitis, Cytoplasmic mislocalization, Pancreatic stone formation",
author = "Shigeru Ko and Sakiko Azuma and Toshiyuki Yoshikawa and Akiko Yamamoto and Kazuhiro Kyokane and Minoru Ko and Hiroshi Ishiguro",
year = "2012",
doi = "10.3389/fphys.2012.00415",
language = "English",
volume = "3 NOV",
journal = "Frontiers in Physiology",
issn = "1664-042X",
publisher = "Frontiers Research Foundation",

}

TY - JOUR

T1 - Molecular mechanisms of pancreatic stone formation in chronic pancreatitis

AU - Ko, Shigeru

AU - Azuma, Sakiko

AU - Yoshikawa, Toshiyuki

AU - Yamamoto, Akiko

AU - Kyokane, Kazuhiro

AU - Ko, Minoru

AU - Ishiguro, Hiroshi

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Bicarbonate secretion

KW - CFTR

KW - Chronic pancreatitis

KW - Cytoplasmic mislocalization

KW - Pancreatic stone formation

UR - http://www.scopus.com/inward/record.url?scp=84870862257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870862257&partnerID=8YFLogxK

U2 - 10.3389/fphys.2012.00415

DO - 10.3389/fphys.2012.00415

M3 - Article

VL - 3 NOV

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

M1 - Article 415

ER -