Roles of solbule (pro)renin receptor in chronic kidney disease

• Project/Area Number: 16H05316
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Ichihara Atsuhiro 東京女子医科大学, 医学部, 教授 (60203105)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 循環器・高血圧 / トランスレーショナルリサーチ / 内科 / 生体分子 / 老化 / 高血圧 / 生理活性 / レニン‐アンジオテンシン系 / Wntシグナル / レニン-アンジオテンシン系

Outline of Final Research Achievements

Double transgenic mice overexpressing soluble (pro)renin receptor and prorenin have been developed mating mice overexpressing soluble (pro)renin receptor and prorenin-overexpressing mice. In the mice, nephropathy is developed and progressed independently their blood pressure. Since soluble (pro)renin receptor is the N-terminal fragment of (pro)renin receptor and releases into the tissue and blood, where the soluble (pro)renin receptor binds prorenin to contribute with the development of nephropathy as a paracrine system. In the near future, new therapy targeting soluble (pro)renin receptor will be developed to inhibit the pathogenesis of chronic kidney diseases.

Academic Significance and Societal Importance of the Research Achievements

慢性腎臓病患者に合併する非感染性疾患(Non-Communicable Disease; NCDs)は、個人及び社会の大きな問題であるため、発症機序の解明と治療法開発は重要である。本研究は、慢性腎臓病で増加する(プロ)レニン受容体[(P)RR]の可溶性部分に着目し、NCDsにおける病態生理学的意義を解明することを目的として実行され、可溶性(P)RRはプロレニンの協力を得て腎障害を発症しNCDs発症に関与することが実証された。本成果により慢性腎臓病の発症と進展に寄与する機構の一部が解明され、可溶性(P)RR を標的とした治療が慢性腎臓病に合併するNCDsへの対策として有効であることが証明された。

Research Products

• [Journal Article] The (pro)renin receptor in health and disease (2019)
  • Author(s): Atsuhiro Ichihara, Midori Sasaki Yatabe
  • Journal Title: Nature Reviews Nephrology Volume: in press
  • Peer Reviewed
• [Journal Article] Elevated (Pro)renin Receptor Expression Contributes to Maintaining Aerobic Metabolism in Growth Hormone Deficiency (2018)
  • Author(s): Seki Yasufumi、Yatabe Midori、Suda Chikahito、Morimoto Satoshi、Ichihara Atsuhiro
  • Journal Title: J Endocr Soc Volume: 2 Issue: 3 Pages: 252-265
  • DOI: 10.1210/js.2017-00447
  • NAID: 120007180401
  • Peer Reviewed
• [Journal Article] Buffering roles of (pro)renin receptor in starvation‐induced autophagy of skeletal muscles (2018)
  • Author(s): Mizuguchi Yuki、Yatabe Midori、Morishima Noriko、Morimoto Satoshi、Ichihara Atsuhiro
  • Journal Title: Physiol Rep Volume: 6 Issue: 5 Pages: e13587-e13587
  • DOI: 10.14814/phy2.13587
  • NAID: 120007180402
  • Peer Reviewed
• [Journal Article] Collecting duct prorenin receptor knockout reduces renal function, increases sodium excretion, and mitigates renal responses in ANG II-induced hypertensive mice (2017)
  • Author(s): Prieto Minolfa C.、Reverte Virginia、Mamenko Mykola、Kuczeriszka Marta、Veiras Luciana C.、Rosales Carla B.、McLellan Matthew、Gentile Oliver、Jensen V. Behrana、Ichihara Atsuhiro、McDonough Alicia A.、Pochynyuk Oleh M.、Gonzalez Alexis A.
  • Journal Title: Am J Physiol Renal Physiol Volume: 313 Issue: 6 Pages: F1243-F1253
  • DOI: 10.1152/ajprenal.00152.2017
  • Peer Reviewed / Int'l Joint Research
• [Presentation] プロレニン受容体の新展開: RASから生命維持へ「(プロ)レニン受容体機能の多様性」 (2019)
  • Author(s): 市原淳弘
  • Organizer: 第92回日本内分泌学会学術総会
• [Presentation] 胎盤栄養膜細胞における低酸素刺激による(プロ)レニン受容体の発現調節 (2017)
  • Author(s): 須田睦仁、谷田部淳一、谷田部緑、遣田美貴、市原淳弘
  • Organizer: 第40回日本高血圧学会総会