Analysis on molecular mechanism of mesangial proliferative glomerulonephritis

• Project/Area Number: 16K10060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: The University of Tokyo
• Principal Investigator: Tsurumi Haruko 東京大学, 医学部附属病院, 登録研究員 (20632269)
• Co-Investigator(Kenkyū-buntansha): 張田 豊 東京大学, 医学部附属病院, 准教授 (10451866) ; 服部 元史 東京女子医科大学, 医学部, 教授 (50192274) ; 神田 祥一郎 東京大学, 医学部附属病院, 助教 (60632651)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 糸球体腎炎 / メサンギウム細胞 / 膜性増殖性糸球体腎炎 / 細胞・組織

Outline of Final Research Achievements

In kidney, glomerular injury results in proliferation and aberrant migration of mesangial cells, which is the pathological characteristic of mesangial proliferative glomerulonephritis. To date, molecular changes that occur in mesangial cells during glomerular injury and their association with the pathogenesis of glomerulonephritis remain largely unclear. We identified expression of a novel molecule(X) in mesangial cells in vivo and in vitro. In kidney tissues from some patients with mesangioproliferative glomerulonephritis, expression of X in glomerlar mesangium was altered. In cultured mesangial cells, X was localized in intracellular vesicles, and involved in endocytosis of extracellular matrix. These result suggested the involvement of novel molecules in pathogenesis of glomerulonephritis.

Academic Significance and Societal Importance of the Research Achievements

小児の腎臓病の代表である糸球体腎炎がどのようにして発症し進展するのかについては不明な点が多い。この研究ではメサンギウム細胞が病的な刺激に応じてどのように変化するのかを明らかにすることで腎炎の発症メカニズムの解明を目指した。メサンギウム細胞に存在する分子を新たに同定し、その分子の発現が一部の腎炎患者で変化すること、またその分子の機能がメサンギウム部分の変化に関連する可能性が示唆された。糸球体腎炎の発症に関連する変化を明らかにした。

Research Products

• [Journal Article] Application of next-generation sequencing technology to diagnosis and treatment of focal segmental glomerulosclerosis (2018)
  • Author(s): Harita Yutaka
  • Journal Title: Clin Exp Nephrol. Volume: 印刷中 Issue: 3 Pages: 491-500
  • DOI: 10.1007/s10157-017-1449-y
  • Peer Reviewed / Open Access
• [Journal Article] 腎疾患に対する遺伝子診断 (2018)
  • Author(s): 張田豊
  • Journal Title: 小児科 Volume: 59 Pages: 1379-1385
• [Journal Article] 小児腎疾患における遺伝子診断の実際 (2018)
  • Author(s): 張田豊
  • Journal Title: 日本小児腎不全学会雑誌 Volume: 38 Pages: 28-33
• [Journal Article] 遺伝子から見た嚢胞性腎疾患 (2018)
  • Author(s): 張田豊
  • Journal Title: じん Volume: 40 Pages: 4-8
• [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] Altered expression of Crb2 in podocytes expands a variation of CRB2 mutations in steroid-resistant nephrotic syndrome. (2017)
  • Author(s): Udagawa T, Jo T, Yanagihara T, Shimizu A, Mitsui J, Tsuji S, Morishita S, Onai R, Miura K, Kanda S, Kajiho Y, Tsurumi H, Oka A, Hattori M, Harita Y.
  • Journal Title: Pediatric Nephrology Volume: 32 Issue: 5 Pages: 801-809
  • DOI: 10.1007/s00467-016-3549-4
  • Peer Reviewed
• [Presentation] 蛋白尿・ネフローゼの発症機序 (2018)
  • Author(s): 張田豊
  • Organizer: 北海道小児腎臓病研究会
  • Invited
• [Presentation] Pathogenic mechanism of childhood idiopathic nephrotic syndrome (2018)
  • Author(s): Yutaka Harita
  • Organizer: ISN FRONTIERS MEETINGS