Pathophygiological Investigations of ATRAP in Renal Tubules on Kidney Injury

• Project/Area Number: 17K16091
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: Uneda Kazushi 横浜市立大学, 医学部, 助教 (90780370)
• Research Collaborator: Tamura Kouichi ; Wakui Hiromichi ; Kinguchi Sho
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: レニン・アンジオテンシン系 / 腎内レニン・アンジオテンシン系 / ATRAP / 高血圧 / 慢性腎臓病 / AT1受容体 / アンジオテンシンII / 循環器・高血圧

Outline of Final Research Achievements

In this study, we generated proximal tubule-specific ATRAP KO mice. Detailed analysis of renal ATRAP expression revealed that ATRAP mRNA expression was decreased by nearly 80% in proximal regions of the nephron in proximal tubule-specific ATRAP KO mice compared with wild-type mice. There were no significant differences in blood pressure, urinary sodium retention and kidney damages between proximal tubule-specific ATRAP KO mice and wild-type mice under conditions of chronic angiotensin II stimulation. These results indicate that renal proximal tubule ATRAP has a minor role in angiotensin-mediated hypertension or kidney injury.

Academic Significance and Societal Importance of the Research Achievements

今回の検討により，近位尿細管特異的ATRAP欠損マウスではアンジオテンシンII依存性高血圧・腎障害の増悪を認めないことが明らかとなった．尿細管のATRAPに関する既報と今回の結果を総合すると，近位尿細管におけるATRAPがアンジオテンシンII依存性高血圧・腎障害の病態に及ぼす影響は少なく，むしろ遠位尿細管に存在するATRAPが重要である可能性が想起された．

Research Products

• [Journal Article] Effects of ATRAP in Renal Proximal Tubules on Angiotensin‐Dependent Hypertension (2019)
  • Author(s): Kinguchi Sho、Wakui Hiromichi、Azushima Kengo、Haruhara Kotaro、Koguchi Tomoyuki、Ohki Kohji、Uneda Kazushi、Matsuda Miyuki、Haku Sona、Yamaji Takahiro、Yamada Takayuki、Kobayashi Ryu、Minegishi Shintaro、Ishigami Tomoaki、Yamashita Akio、Fujikawa Tetsuya、Tamura Kouichi
  • Journal Title: Journal of the American Heart Association Volume: 8 Issue: 8
  • DOI: 10.1161/jaha.119.012395
  • Peer Reviewed / Open Access / Int'l Joint Research