The detection of renal ER stress by a urinary exosomal protein

• Project/Area Number: 25660241
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Veterinary medical science
• Research Institution: University of Miyazaki
• Principal Investigator: IKEDA Masahiro 宮崎大学, 農学部, 教授 (60281218)
• Research Collaborator: MATSUZAKI Toshiyuki ; SONODA Hiroko ; TAKAHASHI Saki ; HIGASHIJIMA Yoshiki ; SHIGEMURA Kanako ; KAITO Ayaha ; KATO Ayaka ; KINOUCHI Minami ; HOSHINO Yuya ; KOGA Moeko ; MIKODA Nobuyuki ; ASVAPROMTADA Siree ; OSHIKAWA Sayaka ; HONBU Anna ; ABDEEN Ahmed
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: エクソソーム / 小胞体ストレス / 腎疾患 / アクアポリン

Outline of Final Research Achievements

Several previous reports have indicated that endoplasmic reticulum (ER) stress is related to renal diseases. In order to find a new biomarker for ER stress in the kidney, we pharmacologically examined the urinary exosomal proteins in rats and cultured cells. Among proteins tested in this study, only the urinary exosomal releasel of AQP1 was markedly decreased by the treatment with tunicamycin (an ER stress inducer). Tunicamycin also decreased the level of AQP1 mRNA in the kidney. When either tunicamycin or thapsigargin (another ER stress inducer) was added to cultured renal proximal tubule cells, down-regulation of AQP1 mRNA was observed. These findings indicates that ER stress decreases the urinary exosomal excretion of AQP1 protein and the underlying mechanism is mediated by lowering the level of renal AQP1 mRNA, suggesting that urinary exosomal AQP1 is a possible biomarker for detection of ER stress in the kidney.

Research Products

• [Journal Article] Acetazolamide enhances the release of urinary exosomal aquaporin-1 (2016)
  • Author(s): Abdeen, S., Sonoda, H., Oshikawa, S., Hoshino, Y., Kondo, H., Ikeda, M.
  • Journal Title: Nephrol. Dial. Transplant. Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] エクソソームと腎疾患 (2015)
  • Author(s): 園田紘子、池田正浩
  • Journal Title: 血管医学 Volume: 16 Pages: 149-157
• [Journal Article] Regulation of aquaporins by vasopressin in the kidney (2015)
  • Author(s): Ikeda, M., Matsuzaki, T.
  • Journal Title: Vitam. Horm. Volume: 98 Pages: 307-337
  • Acknowledgement Compliant
• [Journal Article] Urinary excretion pattern of exosomal aquaporin-2 in rats receiving gentamicin (2014)
  • Author(s): Abdeen, A., Sonoda, H., El-Shawarby, R., Takahashi, S., Ikeda, M.
  • Journal Title: Am. J. Physiol. Renal Physiol. Volume: 307
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 腎疾患におけるエクソソーム (2014)
  • Author(s): 池田正浩、園田紘子
  • Journal Title: Bio Clinica Volume: 29 Pages: 540-543
• [Journal Article] Excretion of urinary exosomal AQP2 in rats is regulated by vasopressin and urinary pH (2013)
  • Author(s): Higashijima, Y., Sonoda, H., Takahashi, S., Kondo, H., Shigemura, K., Ikeda, M.
  • Journal Title: Am. J. Physiol. Renal Physiol. Volume: 305 Issue: 10 Pages: F1412-F1421
  • DOI: 10.1152/ajprenal.00249.2013
  • Peer Reviewed
• [Presentation] 腎線維化モデルラットにおける尿中exosome目抜きタンパク質排泄パターンについての検討 (2016)
  • Author(s): 園田紘子、Asvapromtada, Siree、木内みな美、髙橋早樹、池田正浩
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜市
  • Year and Date: 2016-03-09
• [Presentation] ネフロン癆モデル動物におけるアクアポリン２の腎発現および尿中排泄動態解析 (2016)
  • Author(s): 池田正浩、三小田伸之、押川さやか、園田紘子、松崎利行
  • Organizer: 第26回バゾプレシン研究会
  • Place of Presentation: 新宿区
  • Year and Date: 2016-01-09
• [Presentation] pcyマウス腎におけるaquaporin-2発現パターンについての解析 (2015)
  • Author(s): 三小田伸之、園田紘子、星野雄也、押川さやか、本部杏奈、古賀萌子、池田正浩
  • Organizer: 第158回日本獣医学会
  • Place of Presentation: 十和田市
  • Year and Date: 2015-09-07
• [Presentation] 小胞体ストレス負荷時のアクアポリン1遺伝子発現変化メカニズムの検討 (2014)
  • Author(s): 園田紘子、加藤綾華、重村可南子、髙橋早樹、池田正浩
  • Organizer: 第7回トランスポーター研究会九州部会
  • Place of Presentation: 北九州
  • Year and Date: 2014-11-22
• [Presentation] Negative transcriptional regulation of aquaporin-1 by unfolded protein response (2014)
  • Author(s): Kato, A., Sonoda, H., Shigemura, K., Takahashi, S., Ikeda, M.
  • Organizer: 米国腎臓学会
  • Place of Presentation: フィラデルフィア、米国
  • Year and Date: 2014-11-13 – 2014-11-15
• [Presentation] エクソソームを介したアクアポリン-2尿中排泄のバゾプレシンおよび尿中pHによる調節作用 (2014)
  • Author(s): 池田正浩、東島佳毅、園田紘子
  • Organizer: 第24回 バゾプレシン研究会
  • Place of Presentation: 東京
• [Presentation] 腎疾患バイオマーカーとしての尿中エクソソームAQP (2014)
  • Author(s): 池田正浩、園田紘子
  • Organizer: 日本薬学会第134回年会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] Changes in the excretion of urinary exosomal AQP1 and AQP2 in rats with PAN-induced nephrotic syndrome (2013)
  • Author(s): A. Kaito, H. Sonoda, S. Takahashi, M. Ikeda
  • Organizer: 米国腎臓学会
  • Place of Presentation: アトランタ、米国
• [Remarks]
  • URL: http://www.agr.miyazaki-u.ac.jp/~vet/VetPharmacol/papers.html