Roles of ion channels and water channels in the development of chronic pancreatitis
| Project/Area Number |
18590726
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nagoya University |
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Principal Investigator |
B.H.KO Shigeru Nagoya University, University Hospital, Gastroenterology, Staff (90402578)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIGURO Hiroshi University Hospital, Department of Human Nutrition, Associate Professor (90303651)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Chronic Pancreatitis / Cystic Fibrosis / Guinea-Pig / RNA interference / CFTR / 膵嚢胞線維症 / 慢性腸炎 / パッチクランプ法 |
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| Research Abstract |
[Background and aim]Chronic pancreatitis is a progressive inflammatory disease of the pancreas. Cystic Fibrosis Transmembrane conductance Regulator(CFTR)is a cyclic AMP-regulated chloride channel expressed in the apical plasma membrane of human pancreatic duct cells. Recent evidence suggest that mutation(s) in CFTR is one of the risk factors in developing chronic pancreatitis. The aim of this project was to educidate the roles of ion and water channels in the development of chronic pancreatitis.
[Methods] (1) Genomic DNA was extracted from the leukocytes of the patients. CFTR mutations was identified by direct sequencing. Each exon fragments were amplified by polymerase chain reaction. (2) Genonic DNA of Guinea-pig was isolated from the small intestine. Fragments of guinea pig CFTR was amplified by PCR and directly sequenced. PCR primer sets were designed based on the consensus sequence among human, rat and mouse CFTR. Interlobular ducts were isoloated from the Guinea pig pancreas and cultured overnight. RNA interference was used to reduce the expression of CFTR in guinea pig interlobular ducts.
[Results] (1) In Japanese patient with alcoholic chronic pancreatitis, new mutation in CFTR (L1156F) was identified. L1156F CFTR showed the reduced HCO3- permeability in Xenopus oocytes. (2) Guinea pig CFTR consists of 1481 amino acid residues. Fluid secretary rate in isolated guinea pig pancreatic ducts with CFTR specific RNAi was decreased to half of the rate in control ducts with scrambled RNAi.
[Conclusion] These evidence sugget that reduced expression of CFTR due to the mutations or polymorphisms causes the pancreatic ductal dysfunction and might be the cause of chronic pancreatitis in Japanese.
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Report
(3 results)
Research Products
(60 results)
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[Journal Article] Allochronic biliary strictures appeared in the different regions of the bile duct tree in a patient with autoimmune pancreatitis2007
Author(s)
Ko, SB, Naruse, S, Ishiguro, H, Yoshikawa, T, Yamamoto, T, Futakuchi, S, Goto H
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Journal Title
Pancreas 34
Pages: 479-81
Description
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[Journal Article] Acute tubulointerstitial nephritis associated with long-term gemcitabine therapy2007
Author(s)
Yamamoto, A, Naruse, S, Ito, M, Ishiguro, H, Ko, SB, Yoshikawa, T, Kondo, T, Goto, H
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Journal Title
Description
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[Journal Article] Effect of Skc26a6 deletion on apical, CI/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct2007
Author(s)
Ishiguro, H, Namkung, W, Yamamoto, A, Wang, Z, Worrell, RT, Xu, J, Lee, MG, Soleimani, M
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Journal Title
Am J Physiol Gastrointest Liver Physiol 292
Description
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[Journal Article] Identification of key residues that cause differential gallbladder response to PACAP and VIP in the guinea pig2007
Author(s)
Wei, M, Fujiki, K, Ando, E, Zhang, S, Ozaki, T, Ishiguro, H, Kondo, T, Nokihara, K, Wray, V, Naruse, S
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Journal Title
Am J Physiol Gastrointest Liver Physiol 292
Description
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[Journal Article] Fecal pancreatic elastase : a reproducible marker for severe exocrine pancreatic insufficiency2006
Author(s)
Naruse, 5, Ishiguro, H, Ko, SB, Yoshikawa, T, Yamamoto, T, Yamamoto, A, Futakuchi, S, Goto, H, Saito, Y, Takahashi, S
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Journal Title
J Gastroenterol 41
Pages: 901-8
NAID
Description
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[Journal Article] Sweat chloride measurement with a highly sensitive electrode2006
Author(s)
Naruse, S, Ishiguro, H, Shirota, K, Nakakuki, M, Yamamoto, A, Kondo, T
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Journal Title
Pancreas 33
Pages: 100-100
Description
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[Journal Article] Coupling modes and stoichiometry of CI/HCO3- exchange by slc26a3 and slc26a62006
Author(s)
Shcheynikov, N, Wang, Y, Park, M, Ko, SB, Dorwart, M, Naruse, S, Thomas, PJ, Muallem, S
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Journal Title
J Gen Physiol 127(5)
Pages: 511-24
Description
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[Presentation] Is fine-needle aspiration and trucut core biopsy satisfactory for diagnosing LPSP?2007
Author(s)
Mizuno, N, Ko, S.B.H., Hosoda, W, Hoki, N, Yatabe, Y, Yamao, K
Organizer
International consensus meeting of clinical diagnostic criteria for autoimmune pancreatitis in Kobe. "Clinical questions and answers for international consensus of diagnostic criteria for autoimmune pancreatitis
Place of Presentation
Quality Hotel Kobe
Year and Date
2007-10-17
Description
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[Presentation] Aquaporin 1 water channel protein is overexpressed in the plasma membranes of pancreatic ducts in patients with alcoholic chronic pancreatitis2007
Author(s)
Mizuno, N, Ko, S.B.H., Yatabe, Y, Muallem, S, Yamao, K, Goto, H
Organizer
2nd international symposium on alcoholic liver and pancreatic diseases and cirrhosis. The portpia Hotel Southwing and Kobe international Exhibition Hall 1
Place of Presentation
Kobe, Japan
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Aquaporin 1 water channel protein is overexpressed in the plasma membranes of pancreatic ducts in patients with autoimmune pancreatitis2007
Author(s)
Ko, S.B.H., Mizuno, N, Yatabe, Y, Ishiguro, H, Yoshikawa, T, Yamamoto, A, Naruse, S, Muallem, S, Yamao, K, Goto, H
Organizer
The 5th International conference of aquaporin
Place of Presentation
Nara Centennial Hall
Description
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