A study on ER-stress-induced Fanconi syndrome

• Project/Area Number: 18H02348
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: University of Miyazaki
• Principal Investigator: IKEDA Masahiro 宮崎大学, 農学部, 教授 (60281218)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2019: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 薬理学 / 小胞体ストレス / Fanconi症候群 / 腎虚血再灌流障害

Outline of Final Research Achievements

Although Fanconi syndrome is a multifactorial disease, its clinical features are based on reduced reabsorption of water, solutes, and nutrients in the kidneys, especially in the proximal tubules. So far, the mechanism by which the common symptom of reabsorption deficiency occurs largely unknown. From this study, we have identified a new mechanism of renal endoplasmic reticulum stress for this deficiency. Also, we have shown that at least two gene expressions are directly linked to the symptom. These results provide important information for human and veterinary clinical fields and indicate a new regulatory system for substance metabolism in the kidney.

Academic Significance and Societal Importance of the Research Achievements

Fanconi症候群は、先天性のものから、化学物質誘導型および疾患続発型と多岐の要因で生じる疾患である。しかしながら多くの場合、腎におけるアミノ酸などの再吸収不全という共通の症状を示す。本研究では、この共通の症状を示すメカニズムとして腎の小胞体ストレスを同定している。この成果は、Fanconi症候群の今後の診断・治療法の開発に貢献することに加えて、物質の腎における再吸収や分泌の新しい視座を与え、生理学的にも重要な意味を持つ。

Research Products

• [Journal Article] Decreased excretion of urinary exosomal aquaporin-2 in a puromycin aminonucleoside-induced nephrotic syndrome model. (2020)
  • Author(s): Ahmed, A., Sonoda, H., Kaito, A., Oshikawa-Hori, S., Fujimoto, N., Ikeda, M.
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 12 Pages: 4288-4288
  • DOI: 10.3390/ijms21124288
  • Int'l Joint Research
• [Journal Article] Release of urinary aquaporin-2-bearing extracellular vesicles is decreased in pregnant Japanese Black cattle (2019)
  • Author(s): Sinlapadeelerdkul Thitaporn、Sonoda Hiroko、Uchida Kazuyuki、Kitahara Go、Ikeda Masahiro
  • Journal Title: Journal of Veterinary Medical Science Volume: 81 Issue: 11 Pages: 1609-1615
  • DOI: 10.1292/jvms.19-0276
  • NAID: 130007752558
  • ISSN: 0916-7250, 1347-7439
  • Peer Reviewed
• [Journal Article] Urinary extracellular vesicular release of aquaporins in patients with renal transplantation (2019)
  • Author(s): Oshikawa-Hori Sayaka、Yokota-Ikeda Naoko、Sonoda Hiroko、Ikeda Masahiro
  • Journal Title: BMC Nephrology Volume: 20 Issue: 1 Pages: 216-216
  • DOI: 10.1186/s12882-019-1398-7
  • 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] An Early Decrease in Release of Aquaporin-2 in Urinary Extracellular Vesicles After Cisplatin Treatment in Rats (2019)
  • Author(s): Sonoda Hiroko、Oshikawa-Hori Sayaka、Ikeda Masahiro
  • Journal Title: Cells Volume: 8 Issue: 2 Pages: 139-139
  • DOI: 10.3390/cells8020139
  • Peer Reviewed / Open Access
• [Journal Article] miRNA profiling of urinary exosomes to assess the progression of acute kidney injury (2019)
  • Author(s): Sonoda Hiroko、Lee Byung Rho、Park Ki-Hoon、Nihalani Deepak、Yoon Je-Hyun、Ikeda Masahiro、Kwon Sang-Ho
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 4692-4692
  • DOI: 10.1038/s41598-019-40747-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 尿エクソソームRNA抽出方法の比較検討． (2020)
  • Author(s): 田中彩瑛，園田紘子，池田正浩
  • Organizer: 第63回日本腎臓学会学術総会
• [Presentation] イヌの正常およびFanconi症候群腎におけるaquaporinsの発現パターンの解析． (2020)
  • Author(s): 谷口仁基，園田紘子，平井卓哉，松崎利行，内田和幸，池田正浩
  • Organizer: 第63回日本腎臓学会学術総会
• [Presentation] 小胞体ストレスに着目した腎性ファンコーニ症候群発症メカニズムの検討． (2020)
  • Author(s): 宮元伊織，古賀萌子，園田紘子，星野雄也，藤本成希，池田正浩
  • Organizer: 第163回日本獣医学会学術集会
• [Presentation] Analysis of urinary exosomal RNAs after treatment of rats with an Nrf2 activator. (2020)
  • Author(s): AyaeTanaka, Hiroko Sonoda, YuiSakaguchi, Masahiro Ikeda
  • Organizer: American Society of Nephrology. 54th Annual Meeting
  • Int'l Joint Research
• [Presentation] ネフロン癆モデル動物の腎病態におけるNADPH oxidase 2 の関与について (2019)
  • Author(s): 星野雄也、園田紘子、三小田伸之、池田正浩
  • Organizer: 第71回日本薬理学会西南部会
• [Presentation] 虚血性腎障害ラットにおける尿中細胞外小胞miRNAの網羅的解析 (2019)
  • Author(s): 園田 紘子、Byung Rho Lee、Ki-Hoon Park、Deepak Nihalani、Je-Hyun Yoon、Sang-Ho Kwon、池田 正浩
  • Organizer: 第13回トランスポーター研究会年会
• [Presentation] Decreased release of aquaporin-2 in urinary extracellular vesicles in rats subjected to allogenic kidney transplantation (2018)
  • Author(s): Hiroko Sonoda, Tomonori Nakanishi, Tomoyuki Kabayama, Sayaka Oshikawa, Masahiro Ikeda
  • Organizer: Renal Week 2018, American Society of Nephrology. 52nd Annual Meeting
  • Int'l Joint Research
• [Presentation] 急性腎障害－慢性腎臓病 transitionモデルラットにおける尿中細胞外小胞アクアポリン1および2タンパク質放出パターンについての検討 (2018)
  • Author(s): 園田紘子、シリーアサワプロンターダー、押川さやか、池田正浩
  • Organizer: 第71回日本薬理学会西南部会
• [Book] Role of Exosomes in Biological Communication Systems (2021)
  • Author(s): Abdeen, A., Sonoda, H., Tanaka, A., Ikeda, M.
  • Publisher: Springer Nature Singapore Pte Ltd.
• [Book] 獣医薬理学〈第二版〉 (2021)
  • Author(s): 日本比較薬理学・毒性学会
  • Publisher: 近代出版
  • ISBN: 9784874022702