Investigation of plasma pathogenic factor in Idiopathic nephrotic syndrome using humanized-mouse and flow cytometry analysis of plasma blood cells

• Project/Area Number: 17H06658
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pediatrics
• Research Institution: Tokai University (2018); Tokyo Medical and Dental University (2017)
• Principal Investigator: Udagawa Tomohiro 東海大学, 医学部, 助教 (30623392)
• Project Period (FY): 2017-08-25 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: Nephrotic syndrome / Podocyte / フローサイトメトリー / ポドサイト / 液性因子 / 特発性ネフローゼ症候群 / FACS / 白血球表面抗原 / 末梢血表面抗原 / ネフローゼ症候群 / 末梢血リンパ球表面抗原 / 小児 / 腎疾患 / 血球分画 / ヒト化モデルマウス

Outline of Final Research Achievements

In this present study, to elucidate both a therapeutic target and a permeability factor of the idiopathic nephrotic syndrome in children, we analyzed comprehensive distributions of peripheral blood cells in patient with that disease. It is necessary to analyze a more large samples to get a meaningful result.　We confirmed the alteration of cyteskeletal proteins induced by cytotoxic agent using immortalized podocyte cell line and mouse kidney organoid derived from nephron progenitor cells. This study was thought to become a step of elucidation of pathogenic permeability factor of the idiopathic nephrotic syndrome in children.

Academic Significance and Societal Importance of the Research Achievements

特発性ネフローゼ症候群は原因が未解明な疾患である。ステロイド治療で生じる易感染症、低身長など特徴的副作用を回避するため、病因を解明し新たな治療戦略を確立することが、医学的に重要である。本研究では、特発性ネフローゼ症候群患者の末梢血における血球分画をフローサイトメトリー解析により患者特有の血球分布の傾向を見出した。また機能解析に有用な培養糸球体上皮細胞や腎臓オルガノイドを用いた実験系を確立した。今後患者検体の蓄積と機能解析を進めることで、当初の目的をさらに明らかにすることが期待される。

Research Products

• [Journal Article] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells (2018)
  • Author(s): Udagawa Tomohiro、Harita Yutaka、Miura Kenichiro、Mitsui Jun、Ode Koji L.、Morishita Shinichi、Urae Seiya、Kanda Shoichiro、Kajiho Yuko、Tsurumi Haruko、Ueda Hiroki R.、Tsuji Shoji、Saito Akihiko、Oka Akira
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 2351-2351
  • DOI: 10.1038/s41598-018-20731-4
  • Peer Reviewed / Open Access
• [Journal Article] A review of clinical characteristics and genetic backgrounds in Alport syndrome (2018)
  • Author(s): Nozu K, Nakanishi K, Abe Y, Udagawa T, Okada S, Okamoto T, Kaito H, Kanemoto K, Kobayashi A, Tanaka E, Tanaka K, Hama T, Fujimaru R, Miwa S, Yamamura T, Yamamura N, Horinouchi T, Minamikawa S, Nagata M, Iijima K
  • Journal Title: Clinical and Experimental Nephrology Volume: 23 Issue: 2 Pages: 158-168
  • DOI: 10.1007/s10157-018-1629-4
  • NAID: 120006557458
  • Peer Reviewed / Open Access
• [Presentation] Intracellular trafficking of cubilin is crucial for renal and intestinal endocytosis (2018)
  • Author(s): Tomohiro udagawa, Kenichiro Miura, Seiya Urae, Shoichiro Kanda, Akihiko Saito, Yutaka Harita
  • Organizer: ISN frontier meeting
  • Int'l Joint Research
• [Book] 新 子どもの腎炎・ネフローゼ (2018)
  • Author(s): 編集：伊藤秀一
  • Total Pages: 192
  • Publisher: 東京医学社
  • ISBN: 9784885637025