Pathophysiological significance of Angiotensin Receptor-binding Molecule in progression of renal dysfunction

• Project/Area Number: 26893218
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: OHSAWA masato 横浜市立大学, 医学(系)研究科(研究院), 客員研究員 (60733433)
• Project Period (FY): 2014-08-29 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 腎障害 / レニン・アンジオテンシン系 / 尿細管 / 腎臓 / 高血圧 / アンジオテンシン受容体

Outline of Final Research Achievements

The renin-angiotensin system plays a key role in the maintenance of cardiovascular and renal homeostasis. We previously identified an AT1R-associated protein (ATRAP), which is a molecule directly interacting with the AT1R. The present study was performed to investigate pathophysiological significance of ATRAP in mice model of CKD by employing systemic ATRAP-KO mice. ATRAP-KO mice and their WT mice were subjected to unilateral ureteral obstruction (UUO) or 5/6 nephrectomy (Nx) as CKD model. To examine the effect of ATRAP deficiency, parameters of renal function and fibrosis, proinflammatory cytokine, blood pressure were measured in ATRAP-KO mice and WT mice after UUO or 5/6 Nx. Expression of endogenous ATRAP and proinflammatory cytokine were changed in WT mice after UUO or 5/6 Nx. Accumulating results indicate that ATRAP possibly exerts inhibitory effects on exacerbated AT1R activation in response to pathological stimuli in CKD model.

Research Products

• [Journal Article] TLR4 as a possible key regulator of pathological vascular remodeling by Ang II receptor activation. (2016)
  • Author(s): Tamura K, Kanaoka T, Kobayashi R, Ohki K, Ohsawa M.
  • Journal Title: Hypertens Res. Volume: 38 Issue: 10 Pages: 642-643
  • DOI: 10.1038/hr.2015.65
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Renal Tubule Angiotensin II Type 1 Receptor-Associated Protein Promotes Natriuresis and Inhibits Salt-Sensitive Blood Pressure Elevation. (2015)
  • Author(s): Wakui H, Uneda K, Tamura K, Ohsawa M, Azushima K, Kobayashi R, Ohki K, Dejima T, Kanaoka T, Tsurumi-Ikeya Y, Matsuda M, Haruhara K, Nishiyama A, Yabana M, Fujikawa T, Yamashita A, Umemura S.
  • Journal Title: J Am Heart Assoc. Volume: 19;4(3) Issue: 3 Pages: 1-14
  • DOI: 10.1161/jaha.114.001594
  • Peer Reviewed / Open Access
• [Journal Article] Effects of the oriental herbal medicine Bofu-tsusho-san in obesity hypertension: a multicenter, randomized, parallel-group controlled trial. (2015)
  • Author(s): Azushima K, Tamura K, Haku S, Wakui H, Kanaoka T, Ohsawa M, Uneda K, Kobayashi R, Ohki K, Dejima T, Maeda A, Hashimoto T, Oshikawa J, Kobayashi Y, Nomura K, Azushima C, Takeshita Y, Fujino R, Uchida K, Shibuya K, Ando D, Tokita Y, Fujikawa T, Toya Y, Umemura S.
  • Journal Title: Atherosclerosis. Volume: 240 Issue: 1 Pages: 297-304
  • DOI: 10.1016/j.atherosclerosis.2015.01.025
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] AT1受容体直接結合因子ATRAPのヒト白血球における発現と臨床指標との関連 (2016)
  • Author(s): 春原浩太郎,田村功一,涌井広道,大澤正人,小豆島健護,畝田一司,小林竜,大城光二,金口翔,坪井伸夫,横尾隆,梅村敏
  • Organizer: 第59回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜 （神奈川県横浜市）
  • Year and Date: 2016-06-17
• [Presentation] Effects of deficiency of angiotensin receptor-binding molecule on blood pressure regulation in chronic kidney disease (2015)
  • Author(s): Ryu Kobayashi, Kouichi Tamura, Hiromichi Wakui, Kengo Azushima, Sona Haku, Kazushi Uneda, Kotaro Haruhara, Kohji Ohki, Sho Kinguchi, Masato Ohsawa, Yoshiyuki Toya, Satoshi Umemura
  • Organizer: American Society of Nephrology Kidney Week 2015
  • Place of Presentation: San Diego Convention Cenetr (San Diego, CA, USA)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] Effects of systemic deletion of angiotensin receptor-binding molecule on the aging kidney (2015)
  • Author(s): Kazushi Uneda, Kouichi Tamura, Hiromichi Wakui, Akinobu Maeda, Kengo Azushima, Sona Haku, Ryu Kobayashi, Masato Ohsawa, Yoshiyuki Toya, Satoshi Umemura.
  • Organizer: American Society of Nephrology Kidney Week 2015
  • Place of Presentation: San Diego Convention Cenetr (San Diego, CA, USA)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] The role of renal AT1 receptor-associated protein in salt-sensitive blood pressure regulation (2015)
  • Author(s): Hiromichi Wakui, Kouichi Tamura, Ryu Kobayashi, Kazushi Uneda, Masato Ohsawa, Toru Dejima, Akinobu Maeda, Yoshiyuki Toya, Kotaro Haruhara, Satoshi Umemura.
  • Organizer: American Society of Nephrology Kidney Week 2015
  • Place of Presentation: San Diego Convention Cenetr (San Diego, CA, USA)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] Deletion of the angiotensin II type 1 receptor associated protein enhances renal sodium reabsorption and exacerbates angiotensin II mediated hypertention (2014)
  • Author(s): 大澤 正人
  • Organizer: 第37回日本高血圧学会総会 YIA発表会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] 腎線維化におけるAT1受容体結合因子ATRAPの発現調節についての検討 (2014)
  • Author(s): 大友 優太，涌井 広道，田村 功一，大澤 正人，小豆島 健護，畝田 一司，小林 竜，大城 光二，戸谷 義幸，山下 暁朗，田邊 克幸，前島 洋平，槇野 博史，梅村 敏
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-10-17 – 2014-10-19
• [Presentation] マウス慢性腎臓病病態モデルにおけるAT1受容体結合因子ATRAP発現調節についての検討 (2014)
  • Author(s): 小林 竜，田村 功一，涌井 広道，大澤 正人，小豆島 健護，畝田 一司，大城 光二，戸谷 義幸，山下 暁朗，田邊 克幸，前島 洋平，槇野 博史，梅村 敏
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-10-17 – 2014-10-19