A study on the pathway causing renohepatic crosstalk using systems biology

• Project/Area Number: 16K15047
• 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: SONODA Hiroko ; OSHIKAWA Sayaka
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
• Keywords: 腎肝クロストーク / 多臓器不全 / システムバイオロジー / 腎虚血再灌流障害 / 急性腎不全

Outline of Final Research Achievements

Multi-organ failure is a progressive condition, involving the combined failure of the kidney, liver, and lung, and an effect of acute kidney injury on liver dysfunction (renohepatic crosstalk) has received considerable attention due to the increased risk of poor outcome. In order to propose a specific therapeutic target, in this study we employed experimental models of renohepatic crosstalk and analyzed liver genes and proteins with array and omics technologies, combined with pathway analysis. As a result, we succeeded in finding two novel therapeutic target candidates, CSF2 and adrenomedullin (AM). We anticipate that our present findings will lead to the progress of the understanding of the mechanisms underlying the renohepatic crosstalk, and the development of a pharmacological intervention against this disease condition.

Academic Significance and Societal Importance of the Research Achievements

急性腎不全と肝不全とが合併した場合（腎肝クロストーク）の致死率は高く，その対策は，医学・獣医学両領域において大きな問題となっている．本研究では，モデル動物を用いて検討した結果，この腎肝クロストークの特異的な治療ターゲット候補分子を見出すことに成功した．今後今回の成果などに基づいて，腎肝クロストーク病態の理解が進み，その治療法などが向上して行くことが期待される．

Research Products

• [Journal Article] Involvement of the NADPH oxidase 2 pathway in renal oxidative stress in Aqp11-/- mice (2019)
  • Author(s): Hoshino Yuya、Sonoda Hiroko、Nishimura Ryuji、Mori Kazuya、Ishibashi Kenichi、Ikeda Masahiro
  • Journal Title: Biochemistry and Biophysics Reports Volume: 17 Pages: 169-176
  • DOI: 10.1016/j.bbrep.2019.01.003
  • Peer Reviewed / Open Access
• [Journal Article] A bell‐shaped pattern of urinary aquaporin‐2‐bearing extracellular vesicle release in an experimental model of nephronophthisis (2019)
  • Author(s): Mikoda Nobuyuki、Sonoda Hiroko、Oshikawa Sayaka、Hoshino Yuya、Matsuzaki Toshiyuki、Ikeda Masahiro
  • Journal Title: Physiological Reports Volume: 7 Issue: 9 Pages: e14092-e14092
  • DOI: 10.14814/phy2.14092
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of urinary exosomal release of aquaporin-1 and -2 after renal ischemia-reperfusion in rats (2018)
  • Author(s): Asvapromtada Siree、Sonoda Hiroko、Kinouchi Minami、Oshikawa Sayaka、Takahashi Saki、Hoshino Yuya、Sinlapadeelerdkul Thitaporn、Yokota-Ikeda Naoko、Matsuzaki Toshiyuki、Ikeda Masahiro
  • Journal Title: American Journal of Physiology-Renal Physiology Volume: 314 Issue: 4 Pages: F584-F601
  • DOI: 10.1152/ajprenal.00184.2017
  • Peer Reviewed / Open Access
• [Presentation] Hepatopulmonary syndrome secondary to portal vein thrombosis with chronic hepatitis in a dog (2018)
  • Author(s): Kaneko, Y., Torisu, S., Sonoda, H., Fuke, N., Ikeda, M., Yamaguchi, R., Mizutani, S., Ong, B.H.E., Yamamoto, S., Naganobu, K.
  • Organizer: 43rd World Small Animal Veterinary Association Congress
  • Int'l Joint Research
• [Presentation] 腎小胞体（ER）ストレスはアミノ酸尿症を引き起こす (2017)
  • Author(s): 古賀萌子 加藤綾華 園田紘子 押川さやか 池田正浩
  • Organizer: 第160回日本獣医学会
• [Presentation] 尿中細胞外小胞タンパク質測定による腎移植後の腎aquaporin発現量の推定 (2016)
  • Author(s): 園田紘子、仲西友紀、押川さやか、樺山智之、池田正浩
  • Organizer: 第9回トランスポーター研究会九州部会
  • Place of Presentation: 宮崎市
• [Book] 生体の科学-病態バイオマーカーの”いま” (2016)
  • Author(s): 園田紘子、池田正浩
  • Total Pages: 2
  • Publisher: 医学書院