Clarification of autophagy mechanisms to tracking from exocrine secretory granule membrane

• Project/Area Number: 25461026
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kitasato University
• Principal Investigator: Kawashima Rei 北里大学, 医療衛生学部, 講師 (70392389)
• Co-Investigator(Kenkyū-buntansha): ICHIKAWA Takafumi 北里大学, 医療衛生学部, 教授 (30245378) ; KAWAKAMI Fumitaka 北里大学, 医療衛生学部, 講師 (50511896)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 膵臓 / GP2 / オートファジー / LC3 / 外分泌 / アミラーゼ

Outline of Final Research Achievements

The aim of this study was to reveal whether the glycoprotein2 (GP2) that expressed in zymogen granule membrane of pancreatic acinar cells control the autophagy mechanism. Experiments using GP2 knockout mice, the secretion of pancreatic exocrine digestive enzymes amylase, autophagosomal film forming related protein expression and ER endoplasmic reticulum formed related protein expression were found to have been controlled by the presence or absence of GP2. In conclusion, in the process of autophagy occurs, it was considered to be GP2 molecule relevant at the time of the ER membrane provided.

Research Products

• [Journal Article] Influence of an elemental diet on 5-fluorouracil-induced morphological changes in the mouse salivary gland and colon. (2016)
  • Author(s): Kawashima R., Fujimaki K., Ichikawa T.
  • Journal Title: Support Care Cancer. Volume: 24 Issue: 4 Pages: 1609-1616
  • DOI: 10.1007/s00520-015-2947-7
  • Peer Reviewed / Open Access
• [Journal Article] Elemental diet moderates 5-fluorouracil-induced gastrointestinal mucositis through mucus barrier alteration. (2015)
  • Author(s): Kawashima R, Kawakami F, Maekawa T, Yamamoto H, Koizumi W, Ichikawa T.
  • Journal Title: Cancer Chemother Pharmacol. Volume: 76 Issue: 2 Pages: 269-277
  • DOI: 10.1007/s00280-015-2790-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Chemokine Receptor CCR8 Is Required for Lipopolysaccharide-Triggered Cytokine Production in Mouse Peritoneal Macrophages. (2014)
  • Author(s): Oshio T, Kawashima R, Kawamura YI, Hagiwara T, Mizutani N, Okada T, Otsubo T, Inagaki-Ohara K, Matsukawa A, Haga T, Kakuta S, Iwakura Y, Hosokawa S, Dohi T.
  • Journal Title: PLoS One Volume: 9(4) Issue: 4 Pages: 1-12
  • DOI: 10.1371/journal.pone.0094445
  • Peer Reviewed / Open Access
• [Journal Article] Leucine-rich repeat kinase 2 regulates tau phosphorylation through direct activation of glycogen synthase kinase-3β. (2014)
  • Author(s): Kawakami F, Shimada N, Ohta E, Kagiya G, Kawashima R, Maekawa T, Maruyama H, Ichikawa T.
  • Journal Title: FEBS J. Volume: 281 Issue: 1 Pages: 3-13
  • DOI: 10.1111/febs.12579
  • Peer Reviewed / Open Access
• [Journal Article] Late onset GM2 gangliosidosis presenting with motor neuron disease: an autopsy case. (2014)
  • Author(s): Yokoyama T, Nakamura S, Horiuchi E, Ishiyama M, Kawashima R, Nakamura K, Hasegawa K, Yagishita S.
  • Journal Title: Neuropathology. Volume: 34 Issue: 3 Pages: 304-308
  • DOI: 10.1111/neup.12088
  • Peer Reviewed / Open Access
• [Journal Article] Pathological activation of canonical nuclear-factor κB by synergy of tumor necrosis factor α and TNF-like weak inducer of apoptosis in mouse acute colitis. (2014)
  • Author(s): Dohi T, Kawashima R, Kawamura YI, Otsubo T, Hagiwara T, Amatucci A, Michaelson J, Burkly LC.
  • Journal Title: Cytokine. Volume: 69 Issue: 1 Pages: 14-21
  • DOI: 10.1016/j.cyto.2014.05.001
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic adenoviral gene transfer of a glycosyltransferase for prevention of peritoneal dissemination and metastasis of gastric cancer (2014)
  • Author(s): Kawamura, Y. I., et al.
  • Journal Title: Cancer Gene Therapy Volume: 21 Issue: 10 Pages: 427-433
  • DOI: 10.1038/cgt.2014.46
  • Peer Reviewed / Open Access
• [Journal Article] Microbiota-derived lactate accelerates colon epithelial cell turnover in starvation-refed mice. (2013)
  • Author(s): Okada T1, Fukuda S, Hase K, Nishiumi S, Izumi Y, Yoshida M, Hagiwara T, Kawashima R, Yamazaki M, Oshio T, Otsubo T, Inagaki-Ohara K, Kakimoto K, Higuchi K, Kawamura YI, Ohno H, Dohi T.
  • Journal Title: Nat Commun. Volume: 1654 Pages: 4-20
  • Peer Reviewed
• [Presentation] パーキンソン病原因分子LRRK2とp53の相互作用とリン酸化 (2015)
  • Author(s): 川上文貴、川島麗、前川達則
  • Organizer: MBM2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 5-FU起因性消化管粘膜傷害において成分栄養剤が生体防御機構に与える影響 (2015)
  • Author(s): 川島麗、雲井利亮、曽根暦美
  • Organizer: MBM2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 神経細胞LRRK2を介する腸管上皮細胞調節機構の解析 (2015)
  • Author(s): 山下博徳、前川達則、川島麗
  • Organizer: MBM2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 消化管運動におけるLRRK2の機能解析 (2015)
  • Author(s): 津島博道、前川達則、川島麗
  • Organizer: MBM2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] ラット唾液ムチンを認識するモノクローナル抗体の作製 (2015)
  • Author(s): 合田瑞紀、飯田泰広、川島麗
  • Organizer: MBM2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] 腸管神経LRRK2を介する腸管上皮細胞調節機構の解析 (2015)
  • Author(s): 山下博徳、前川達則、川島麗
  • Organizer: 第28回北里大学バイオサイエンスフォーラム
  • Place of Presentation: 北里大学（神奈川県相模原市）
  • Year and Date: 2015-08-06
• [Presentation] 消化管運動におけるLRRK2の機能解析 (2015)
  • Author(s): 津島博道、山下博徳、川島麗
  • Organizer: 第28回北里大学バイオサイエンスフォーラム
  • Place of Presentation: 北里大学（神奈川県相模原市）
  • Year and Date: 2015-08-06
• [Presentation] 5-Fluorouracil起因性消化管粘膜傷害に対する成分栄養剤の効果 (2014)
  • Author(s): 川島麗、雲井利亮、菅原節子、前川達則、川上文貴、石原和彦、市川尊文
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] ラット小腸ムチン分子種を認識するモノクローナル抗体 (2014)
  • Author(s): 小坂裕、飯田泰広、川島麗、五艘行信、石原和彦、市川尊文、栗原誠
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 5-Fluorouracil起因性消化管粘膜傷害において成分栄養剤がムチン分泌機能に与える影響 (2014)
  • Author(s): 雲井利亮、川島麗、曽根暦美、杉元くるみ、星菜奈海、坂井唯人、菅原節子、前川達則、川上文貴、市川尊文
  • Organizer: 第26回北里大学バイオサイエンスフォーラム
  • Place of Presentation: 北里大学相模原キャンパス（神奈川県相模原市）
  • Year and Date: 2014-08-21 – 2014-08-22
• [Presentation] TWEAK/Fn14 pathway promotes chronic colitis and fibrosis mediated by IL-13-TSLP axis.
  • Author(s): Dohi T, Kawashima R.
  • Organizer: IMMUNOLOGY 2013
  • Place of Presentation: Hawaii convention center（Honolulu, Hawaii)
• [Presentation] LRRK2によるGSK-3βの活性化を介したタウのリン酸化調節
  • Author(s): 川上文貴、川島麗、前川達則、嶋山ひとみ、石原和彦、市川尊文
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] ット小腸ムチンに対するモノクローナル抗体の作製
  • Author(s): 小坂裕、臼玉洋平、飯田泰広、川島麗、五艘行信、石原和彦、市川尊文、栗原誠
  • Organizer: 第86回日本生化学会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] わかめの脂肪代謝に及ぼす影響についての検討
  • Author(s): 丸山弘子、黄純聰、川島麗、木村武俊、吉永恵子、加原卓一、仲野隆久
  • Organizer: 第12回日本応用藻類学会
  • Place of Presentation: 東京海洋大学 楽水会館大会議室（東京都港区）