Role of CFTR gene expression in the pathogenesis of chronic pancreatitis : regulation by non-coding region

• Project/Area Number: 19590758
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Nagoya University
• Principal Investigator: ISHIGURO Hiroshi Nagoya University, 総合保健体育科学センター, 准教授 (90303651)
• Co-Investigator(Kenkyū-buntansha): YAMAMOTO Akiko 名古屋大学, 総合保健体育科学センター, 助教 (60402385) ; FUJIKI Kotoyo 名古屋学芸大学, 管理栄養学部, 講師 (50454450)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: CFTR / 慢性膵炎 / プロモーター領域 / 非翻訳領域 / 遺伝子変異 / 遺伝子多型 / 汗中Cl-濃度 / 指先汗クロライド試験 / 転写調節 / 汗中Cl^-濃度

Research Abstract

嚢胞線維症の原因遺伝子であるCFTR は、上皮細胞に発現し陰イオンチャネルとして機能する。CFTRの機能低下は汗中のクロール濃度の高値によって評価できる。我々の以前の研究では、慢性膵炎患者の約半数でCFTRの機能低下が示唆されたが、CFTR遺伝子の翻訳領域の変異/多型とは必ずしも一致しなかった。本研究では、CFTR遺伝子のプロモーター領域(翻訳領域の上流約2kb)の遺伝子解析を行い、慢性膵炎患者に特有な変異-1523G/Aと-790ΔTを同定した。

Research Products

• [Journal Article] Functional coupling of apical Cl-/HCO_3^- exchange with CFTR in stimulated HCO_3^- secretion by guinea pig interlobular pancreatic duct (2009)
  • Author(s): Stewart AK, Yamamoto A, Nakakuki M, Kondo T, Alper SL, Ishiguro H.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol [Epub ahead of print]
  • Peer Reviewed
• [Journal Article] CFTR functions as a bicarbonate channel in pancreatic duct cells (2009)
  • Author(s): Ishiguro H, Steward MC, Naruse S, Ko SB, Goto H, Case RM, Kondo T, Yamamoto A.
  • Journal Title: J Gen Physiol 133(3) Pages: 315-26
  • Peer Reviewed
• [Journal Article] CFTR functions as a bicarbonate channel in pancreatic duot cells. (2009)
  • Author(s): Ishiguro H, Steward MC, Naruse S, Ko SBH, Goto H, Case RM, Kondo T, Yamamoto A.
  • Journal Title: J Gen Physiol 133 Pages: 315-326
  • Peer Reviewed
• [Journal Article] 汗中クロライド濃度の簡便な測定法の開発 (2008)
  • Author(s): 中莖みゆき、石黒洋、代田桂一、山本明子、洪繁、後藤秀実、藤木理代、近藤孝晴、遠藤彰、成瀬達
  • Journal Title: 膵臓 23(4) Pages: 486-493
  • NAID: 10024367756
  • Peer Reviewed
• [Journal Article] ΔFマウスとslc26a6 nullマウスを用いた (2008)
  • Author(s): 石黒洋、山本明子、近藤孝晴
  • Journal Title: 膵HCO_3^-分泌機構の解析 23(1) Pages: 25-30
  • Peer Reviewed
• [Journal Article] 汗中クロライド濃度の簡便な測定法の開発 (2008)
  • Author(s): 中莖みゆき, 石黒洋, 代田桂一, 山本明子, 洪繁, 後藤秀実, 藤木理代, 近藤孝晴, 遠藤彰, 成瀬達
  • Journal Title: 膵臓 23 Pages: 486-493
  • NAID: 10024367756
  • Peer Reviewed
• [Journal Article] △Fマウスとslc26a6 nullマウスを用いた膵HC0_3^-分泌機構の解析 (2008)
  • Author(s): 石黒洋, 山本明子, 近藤孝晴
  • Journal Title: 膵臓 23 Pages: 25-30
  • Peer Reviewed
• [Journal Article] Cystic fibrosis transmembrane conductance regulator and SLC26 transporters in HCO_3^-secretion by pancreatic duct cells (2007)
  • Author(s): Ishiguro H, Steward M, Naruse S.
  • Journal Title: Sheng Li Xue Bao-Acta Physiologica Sinica (Chinese Journal of Physiology) 59(4) Pages: 465-76
  • Peer Reviewed
• [Journal Article] Effect of Slc26a6 deletion on apical Cl^-/HCO_3^-exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct (2007)
  • Author(s): Ishiguro H, Namkung W, Yamamoto A, Wang Z, Worrell RT, Xu J, Lee MG, Soleimani M.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol 292(1)
  • Peer Reviewed
• [Journal Article] Is genetic analysis helpful for diagnosing chronic pancreatitis in its early stage? (2007)
  • Author(s): Naruse S, Fujiki K, Ishiguro H.
  • Journal Title: J Gastroenterol 42 Suppl 17 Pages: 60-5
  • NAID: 10018540047
  • Peer Reviewed
• [Journal Article] Cystic fibrosis transmembrane conductance regulator and SLC26 transp orters in HCO_<3-> secretion by pancreatic duct cells. (2007)
  • Author(s): Ishiguro H, Steward M, Naruse S.
  • Journal Title: Sheng Li Xue Bao(Chinese Journal of Physiology) 59 Pages: 465-476
  • Peer Reviewed
• [Journal Article] Effect of Slc26a6 deletion on apical Cl^-/HCO_<3>- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct. (2007)
  • Author(s): Ishiguro H, Namkung W, Yamamoto A, Wang Z, Worrell RT, Xu J, Lee MG, Soleimani M.
  • Journal Title: Am J Physiol Gastrointest Liver Physiol 292 Pages: 447-455
  • Peer Reviewed
• [Journal Article] Is genetic analysis helpful for diagnosing chronic pancreatitis in its early stage? (2007)
  • Author(s): Naruse S, Fujiki K, Ishiguro H
  • Journal Title: J Gastroenterol 42(Suppl 17) Pages: 60-65
  • NAID: 10018540047
  • Peer Reviewed
• [Presentation] Regulatory interaction of the apical Na+-H+ exchange in HCO_3^- secretion in mouse pancreatic duct cells. (2008)
  • Author(s): Yamamoto A, Ishiguro H, Kondo T.
  • Organizer: 16th United European Gastroenterology Week
  • Place of Presentation: Vienna
  • Year and Date: 2008-10-22
• [Presentation] The genetic background of CFTR and ALDH2 is related to alcoholic chronic pancreatitis in Japanese (2008)
  • Author(s): Fujiki K, Ishiguro H, Nakakuki M, Yamamoto A, Kitagawa M, Kondo T, Naruse S.
  • Organizer: 16th United European Gastroenterology Week
  • Place of Presentation: Vienna
  • Year and Date: 2008-10-22
• [Presentation] The genetic background of CFTR and ALDH2 is related to alcoholic chronic pancreat it is in Japanese. (2008)
  • Author(s): Fujiki K, Ishiguro H, Nakakuki M, Yamamoto A, Kitagawa M, Kondo T, Naruse S.
  • Organizer: 16th United European Gastroenterology Week
  • Place of Presentation: ウィーン
  • Year and Date: 2008-10-22
• [Presentation] アルコール性慢性膵炎患者のCFTRおよびALDH2遺伝子多型の解析(要望演題) (2008)
  • Author(s): 藤木理代、石黒 洋、中莖みゆき、山本明子、北川元二、近藤孝晴、成瀬達
  • Organizer: 第39回日本膵臓学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-07-30
• [Presentation] slc26a6ノックアウトマウスから単離した小葉間膵管の重炭酸イオン輸送 (2008)
  • Author(s): 石黒洋、山本明子、近藤孝晴
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-25
• [Presentation] Interaction between cystic fibrosis transmembrane conductance regulator and Na+-H+ exchange in mouse pancreatic ducts (2007)
  • Author(s): Yamamoto A, Ishiguro H, Ko SB, Naruse S, Kondo T.
  • Organizer: Asian Pacific Digestive Week 2007
  • Place of Presentation: Kobe
  • Year and Date: 2007-10-19
• [Presentation] Role of SLC26A6 in ductal HCO_3^- secretion. Symposium "Frontiers in Exocrine Pancreatic Physiology and Pathophysiology" (2007)
  • Author(s): Ishiguro H
  • Organizer: European Pancreatic Club 2007
  • Place of Presentation: Newcastle-Gateshead
  • Year and Date: 2007-07-07
• [Presentation] ΔFマウスおよびSlc26a6ノックアウトマウスから単離した小葉間膵管の重炭酸イオン輸送ワークショップ「膵研究モデルの作成、選択、適用」 (2007)
  • Author(s): 石黒洋、山本明子、近藤孝晴
  • Organizer: 第38回日本膵臓学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-06-29
• [Book] 膵嚢胞線維症の診療の手引き (2008)
  • Author(s): 大槻眞、成瀬達、近藤孝晴、石黒洋、山本明子、洪繁(他)
  • Total Pages: 74
  • Publisher: アークメディア(東京)
• [Book] 胆嚢胞線維症の診療の手引き (2008)
  • Author(s): 大槻波, 成瀬達, 石黒洋, 山本明子, 藤木理代, 他
  • Total Pages: 74
  • Publisher: アークメディア
• [Book] CFTRの機能異常と慢性膵炎 (2007)
  • Author(s): 石黒洋、近藤孝晴、山本明子、成瀬達
  • Publisher: Annual Review消化器2007(中外医学社)