The roles of mislocalization of membrane proteins in the development of chronic pancreatitis

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590807
• 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: KO Shigeru Nagoya University, 医学部附属病院, 助教 (90402578)
• Co-Investigator(Kenkyū-buntansha): ISHIGURO Hiroshi 名古屋大学, 総合保健体育科学センター, 教授 (90303651) ; YAMAMOTO Akiko 名古屋大学, 総合保健体育科学センター, 准教授 (60402385) ; GOTO Hidemi 名古屋大学, 大学院・医学系研究科, 教授 (10215501) ; MIZUNO Nobumasa 愛知県がんセンター, 腫瘍免疫部, 研究員 (80399592)
• Project Period (FY): 2008 – 2010
• Keywords: 慢性膵炎 / 膜蛋白 / 細胞内局在 / CFTR / AQP

Research Abstract

Chronic pancreatitis is a progressive disease of the pancreas. Accumulating evidence suggests that CFTR channel, which is expressed in the apical plasma membrane of pancreatic duct cells, is one of the factors that cause pancreatitis. However, it remains unknown how CFTR dysfunction cause pancreatitis. In chronic pancreatitis, CFTR is largely mislocalized in the cytoplasm of pancreatic duct cells. When CFTR expression was reduced by RNA interference in isolated guinea-pig pancreatic duct cells, pancreatic fluid secretion was remarkably reduce to ～50% of control. These findings indicate that CFTR expression directly regulates the fluid secretion from pancreatic duct cells and therefore CFTR dysfunction is one of the mechanisms to develop chronic pancreatitis.

Research Products

• [Journal Article] Intravenous fluid therapy successfully prevents renal injury by gemcitabine in patients with pancreatic cancer. (2011)
  • Author(s): Ko SB, Azuma S, Anzai N, Yamamoto A, Mizuno N, Kamimura K, Ishiguro H, Goto H.
  • Journal Title: Pancreas in press
  • Peer Reviewed
• [Journal Article] How fast can pancreatic cancer grow? A case of pancreatic carcinoma developed within 5 months after a negative examination to the advanced stage with multiple liver and bone metastases. (2011)
  • Author(s): Ko SB, Goto H
  • Journal Title: Pancreas 40(2) Pages: 318-319
  • Peer Reviewed
• [Journal Article] Corticosteroids correct aberrant CFTR localization in the duct and regenerate acinar cells in autoimmune pancreatitis. (2010)
  • Author(s): Ko SB, Mizuno N, Yatabe Y, Yoshikawa T, Ishiguro H, Yamamoto A, Azuma S, Naruse S, Yamao K, Muallem S, Goto H.
  • Journal Title: Gastroenterology. 138(5) Pages: 1988-1996
  • Peer Reviewed
• [Journal Article] Glucose transport in interlobular ducts isolated from rat pancreas. (2009)
  • Author(s): Futakuchi S, Ishiguro H, Naruse S, Ko SB, Fujiki K, Yamamoto A, Nakakuki M, Song Y, Steward MC, Kondo T, Goto H.
  • Journal Title: J Med Invest 56 Pages: 308-311
• [Journal Article] Aquaporin 1 water channel is overexpressedin the plasma membranes of pancreatic ducts in patients with autoimmune pancreatitis. (2009)
  • Author(s): Ko SB, Mizuno N, Yatabe Y, Yoshikawa T, Ishiguro H, Yamamoto A, Azuma S, Naruse S, Yamao K, Muallem S, Goto H.
  • Journal Title: J Med Invest 56 Pages: 318-321
• [Journal Article] High glucose inhibits HCO3- and fluid secretion in rat pancreatic ducts. (2009)
  • Author(s): Futakuchi S, Ishiguro H, Naruse S, Ko SB, Fujiki K, Yamamoto A, Nakakuki M, Song Y, Steward MC, Kondo T, Goto H.
  • Journal Title: Pflugers Arch. 459 Pages: 215-226
  • Peer Reviewed
• [Journal Article] Lactoferrin in gastrointestinal disease. (2009)
  • Author(s): Hayakawa T, Jin CX, Ko SB, Kitagawa M, Ishiguro H.
  • Journal Title: Intern Med. 48(15) Pages: 1251-1254
  • Peer Reviewed
• [Journal Article] Pancreas-specific aquaporin 12 null mice showed increased susceptibility to caerulein-induced acute pancreatitis. (2009)
  • Author(s): Ohta E, Itoh T, Nemoto T, Kumagai J, Ko SB, Ishibashi K, Ohno M, Uchida K, Ohta A, Sohara E, Uchida S, Sasaki S, Rai T.
  • Journal Title: Am J Physiol Cell Physiol. 297 Pages: 1368-1378
  • Peer Reviewed
• [Journal Article] Histological diagnosis of autoimmune pancreatitis using EUS-guided trucut biopsy : a comparison study with EUS-FNA. (2009)
  • Author(s): Mizuno N, Bhatia V, Hosoda W, Sawaki A, Hoki N, Hara K, Takagi T, Ko SB, Yatabe Y, Goto H, Yamao K.
  • Journal Title: J Gastroenterol. 44(7) Pages: 742-50
  • Peer Reviewed
• [Journal Article] Standard steroid therapy for autoimmune pancreatitis. (2009)
  • Author(s): Kamisawa T, Shimosegawa T, Okazaki K, Nishino T, Watanabe H, Kanno A, Okumura F, Nishikawa T, Kobayashi K, Ichiya T, Takatori H, Yamakita K, Kubota K, Hamano H, Okamura K, Hirano K, Ito T, Ko S, Omata M.
  • Journal Title: Gut. 58(11) Pages: 1504-1507
  • 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 Pages: 315-326
  • Peer Reviewed
• [Journal Article] Observation of deworming process in intestinal Diphyllobothrium latum parasitism by gastrografin injection into jejunum through double-balloon enteroscope. (2008)
  • Author(s): Ko SB, et al.
  • Journal Title: Am J Gastroenterol. 103(8) Pages: 2149-50
  • Peer Reviewed
• [Journal Article] Research Committee of Intractable Pancreatic Diseases provided by the Ministry of Health, Labour and Welfare of Japan and the Korean Society of Pancreatobiliary Diseases. Asian diagnostic criteria for autoimmune pancreatitis : consensus of the Japan-Korea Symposium on Autoimmune Pancreatitis. (2008)
  • Author(s): Otsuki M, Chung JB, Okazaki K, Kim MH, Kamisawa T, Kawa S, Park SW, Shimosegawa T, Lee K, Ito T, Nishimori I, Notohara K, Naruse S, Ko SB, Kihara Y
  • Journal Title: J Gastroenterol. 43(6) Pages: 403-408
  • Peer Reviewed
• [Presentation] 機能及び組織からみた1型および2型自己免疫性膵炎の病態 (2011)
  • Author(s): 水野伸匡、山雄健次、洪繁
  • Organizer: 厚生労働省科学研究費補助金難治性疾患克服研究事業・IgG4関連全身硬化性疾患の診断確立と治療法開発に関する研究、平成22年第二回総会
  • Place of Presentation: メルパルク京都
  • Year and Date: 2011-02-01
• [Presentation] 自己免疫性膵炎の組織回復における幹・前駆細胞の関与 (2011)
  • Author(s): 水野伸匡、洪繁, 他
  • Organizer: 厚生労働省科学研究費補助金難治性疾患克服研究事業・難治性膵疾患に関する調査研究班、平成22年度第二回研究報告会
  • Place of Presentation: トウキョウステーションコンファレンス
  • Year and Date: 2011-01-21
• [Presentation] 日本人のう胞線維症1症例のCFTR遺伝子解析 (2011)
  • Author(s): 石黒洋、洪繁, 他
  • Organizer: 厚生労働省科学研究費補助金難治性疾患克服研究事業・難治性膵疾患に関する調査研究班、平成22年度第二回研究報告会
  • Place of Presentation: トウキョウステーションコンファレンス
  • Year and Date: 2011-01-21
• [Presentation] 自己免疫性膵炎患者におけるステロイド治療による膵外分泌機能の長期予後 (2010)
  • Author(s): 水野伸匡、洪繁、山雄健次
  • Organizer: 日本消化器関連学会週間2010パネルディスカッション-5自己免疫性膵炎の治療と予後
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 20101013-20101016
• [Presentation] 成人膵における膵幹/幹細胞の局在と自己免疫性膵炎の膵組織回復における幹/前駆細胞の関与 (2010)
  • Author(s): 洪繁、水野伸匡、後藤秀実
  • Organizer: 日本消化器関連学会週間2010ワークショップ16肝胆膵疾患と組織幹細胞/progenitor cell:病態解析と治療戦略
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 20101013-20101016
• [Presentation] ステロイド治療による自己免疫性膵炎の機能回復における膵幹/前駆細胞の関与 (2010)
  • Author(s): 洪繁、水野伸匡、後藤秀実
  • Organizer: 日本消化器関連学会週間2010パネルディスカッション15膵炎の基礎と臨床
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 20101013-20101016
• [Presentation] Corticosteroid correct aberrant cystic fibrosis transmembrane conductance regulator localization in the duct and regenerate acinar cells in autoimmune pancreatitis. (2010)
  • Author(s): Ko SB, Mizuno N, Yatabe Y, Yoshikawa T, Ishiguro H, Yamamoto A, Azuma S, Nause S, Yamao K, Muallem S, Goto H.
  • Organizer: International Association of Pancreatology at Fukuoka
  • Year and Date: 20100711-20100713
• [Presentation] Corticosteroid correct aberrant cystic fibrosis transmembrane conductance regulator localization in the duct and regenerate acinar cells in autoimmune pancreatitis. (2010)
  • Author(s): Ko SB, Mizuno N, Yatabe Y, Yoshikawa T, Ishiguro H, Yamamoto A, Azuma S, Nause S, Yamao K, Muallem S, Goto H.
  • Organizer: European Pancreatic Club meeting at Stockholm
  • Place of Presentation: Sweden
  • Year and Date: 20100617-20100619
• [Presentation] Histological Diagnosis of Autoimmune Pancreatitis Using EUS-Guided Trucut Biopsy : A Comparison Study With EUS-FNA. (2009)
  • Author(s): Mizuno N, Hosoda W, Bhatia V, Hara K, Sawaki A, Hijioka S, Imamura H, Ko SB, Yatabe Y, Goto H, Yamao K.
  • Organizer: Joint 40th Anniversary meeting of American Pancreatic Association and Japan Pancreas Society
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 20091104-20091107
• [Presentation] Pancreatic ductal HCO3. secretion in a disease-implication for the role of ion channels and transporters (2009)
  • Author(s): Ko SB
  • Organizer: PAT-CVR interanational Symposium, Speaker,Symposim VPhysiological institute
  • Place of Presentation: Okazaki, Japan
  • Year and Date: 20090804-20090806
• [Presentation] 膵炎のステロイド治療における膵組織再生と血球系幹細胞マーカーCD133の発現 (2009)
  • Author(s): 洪繁、水野伸匡、山雄健次、後藤秀実
  • Organizer: 第40回日本膵臓学会大会シンポジウム1、「慢性膵炎の基礎研究における最近の進歩-新しい診断と治療法の開発に向けての展望-」
  • Place of Presentation: 京王プラザホテル、東京
  • Year and Date: 20090730-20090731
• [Presentation] Aquaporin Water channel protein is overexpressed in the plasma membranes of pancreatic ducts in patients with autoimmune chronic pancreatitis. (2009)
  • Author(s): Ko SB, Mizuno N, Yatabe Y, Ishiguro H, Azuma S, Yoshikawa T, Yamamoto A, Naruse S, Yamao K, Muallem S, Goto H.
  • Organizer: Symposium 3, Speaker Aquaporin and Ion channel/Transporter : Physiology and Disease : Part II International Symposium in Exocrine Secretion at Tokushima, 2009
  • Place of Presentation: Tokushima University, Japan
  • Year and Date: 20090723-20090725
• [Presentation] 膵癌治療薬ゲムシタビンによる高尿酸血症副作用における尿酸トランスポーターURAT1の役割 (2009)
  • Author(s): 洪繁、東祥子、山本明子、石黒洋、後藤秀実
  • Organizer: 第4回トランスポーター研究会
  • Place of Presentation: シンポジウムII、東京大学
  • Year and Date: 20090523-20090524
• [Presentation] 塩酸ゲムシタビン腎症予防における輸液療法の有用性 (2009)
  • Author(s): 洪繁、石黒洋、山本明子、東祥子、後藤秀実
  • Organizer: 日本消化器病学会東海支部第111回例会シンポジウム「肝胆膵悪性腫瘍に対する診断と治療の進歩」
  • Place of Presentation: 名古屋国際会議場、名古屋市
  • Year and Date: 2009-12-05
• [Presentation] 自己免疫性膵炎の消化吸収障害とその対策 (2009)
  • Author(s): 洪繁、水野伸匡、後藤秀実
  • Organizer: 第51回日本消化器病学会大会、2009/10/14-17消化吸収学会、消化器病学会共催ワークショップ16:膵・胆道疾患における消化吸収障害とその対策
  • Place of Presentation: 国立京都国際会館、京都府
  • Year and Date: 2009-10-16
• [Presentation] 自己免疫性膵炎(AIP)のステロイド治療による膵外分泌機能回復と膵幹/前駆細胞の同定 (2009)
  • Author(s): 水野伸匡、洪繁、山雄健次
  • Organizer: JDDW2009、消化器病学会2009/10/14-17ワークショップ20:自己免疫性膵炎関連疾患の病因病態
  • Place of Presentation: グランドプリンスホテル京都、京都府
  • Year and Date: 2009-10-16
• [Presentation] RNA干渉法を用いたモルモットCFTR機能の解析 (2008)
  • Author(s): 洪繁、山本明子、宋海珍、石黒洋、後藤秀実
  • Organizer: 第3回トランスポーター研究会
  • Place of Presentation: 京都大学、薬学部
  • Year and Date: 20080607-20080608
• [Presentation] 膵外分泌機能からみた自己免疫性膵炎に対するステロイド投与の意義 (2008)
  • Author(s): 洪繁、水野伸匡、後藤秀実
  • Organizer: 第50回日本消化器病学会大会シンポジウム11 「自己免疫性膵炎の診断、治療:ステロイド投与の意義」
  • Place of Presentation: 東京都、グランドプリンスホテル
  • Year and Date: 2008-10-01
• [Presentation] CFTR-SLC26輸送体複合体のイオン輸送機能における低分子量G蛋白質の役割文部省科学研究費補助金特定領域生体膜トランスポートソームの分子機構と生理機能 (2008)
  • Author(s): 洪繁、石黒洋、山本明子、有村奈利子、相馬義郎、後藤秀実
  • Organizer: 平成20年度第一回班会議
  • Place of Presentation: 淡路夢舞台国際会議場、兵庫県淡路市
  • Year and Date: 2008-09-26
• [Presentation] 自己免疫性膵炎および特発性慢性膵炎における膵内・外分泌機能相関 (2008)
  • Author(s): 水野伸匡、洪繁、後藤秀実、山雄健次
  • Organizer: 第39回日本膵臓学会大会ワークショップ4「膵内・外分泌の基礎と臨床:相互相関をめぐって」
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2008-07-31
• [Presentation] Aquaporin Water channel protein is overexpressed in the plasma membranes of pancreatic ducts in patients with autoimmune chronic pancreatitis. (2008)
  • Author(s): Ko SB, Mizuno N, Yatabe Y, Ishiguro H, Yoshikawa T, Yamamoto A, Naruse S, Muallem S, Yamao K, Goto H.
  • Organizer: Autoimmune pancreatitis Summit AIP 2008
  • Place of Presentation: Seoul, South Korea
  • Year and Date: 2008-07-04
• [Presentation] Aquaporin Water channel protein is overexpressed in the plasma membranes of pancreatic ducts in patients with autoimmune chronic pancreatitis. (2008)
  • Author(s): Ko SB, Mizuno N, Yatabe Y, Ishiguro H, Yoshikawa T, Yamamoto A, Naruse S, Muallem S, Yamao K, Goto H
  • Organizer: The international Pancretic Research Forum
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2008-03-22