The functional role of angiotensin receptor-binding molecule in chronic kidney disease and metabolic disorders.

• Project/Area Number: 22890150
• 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: WAKUI Hiromichi 横浜市立大学, 附属病院, 助教 (10587330)
• Research Collaborator: TAMURA Kouichi 横浜市立大学, 医学部, 准教授 (40285143) ; UMEMURA Satoshi 横浜市立大学, 医学研究科, 教授 (00128589)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,068,000 (Direct Cost: ¥2,360,000、Indirect Cost: ¥708,000); Fiscal Year 2011: ¥1,469,000 (Direct Cost: ¥1,130,000、Indirect Cost: ¥339,000); Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
• Keywords: レニンアンジオテンシン系 / 受容体 / 慢性腎臓病 / 高血圧 / メタボリック症候群 / レニン-アンジオテンシン系

Research Abstract

The AT1 receptor(AT1R)-associated protein(ATRAP) is a molecule specifically interacting with the carboxyl-terminal domain of AT1R. In the present study, we demonstrated that a kidney-specific regulatory balancing of ATRAP and AT1R expression may be involved in the modulation of AT1R signaling at local tissue sites and also in the pathophysiology of hypertension and its associated renal injury. Furthermore, we showed that AT1R blockade, ARB, attenuated hypertension and renal injury concomitant with the sustained recovery of renal ATRAP expression. These results suggest that ATRAP can be a novel therapeutic target in chronic kidney disease.

Research Products

• [Journal Article] Mice lacking hypertension candidate gene ATP2B1 in vascular smooth muscle cells show significant blood pressure elevation (2012)
  • Author(s): Hiromichi Wakui, et al
  • Journal Title: Hypertension Volume: 59 Pages: 854-860
  • Peer Reviewed
• [Journal Article] Prepubertal angiotensin blockade exerts long-term therapeutic effect through sustained ATRAP activation in salt-sensitive hypertensive rats (2011)
  • Author(s): Dejima T, Tamura K, Wakui H, Maeda A, Ohsawa M, Kanaoka T, Haku S, Kengo A, Masuda SI, Shigenaga AI, Azuma K, Matsuda M, Yabana M, Hirose T, Uchino K, Kimura K, Nagashima Y, Umemura S.
  • Journal Title: J Hypertens Volume: 29 Pages: 1919-29
  • Peer Reviewed
• [Journal Article] Effects of multiple factorial intervention on ambulatory BP profile and renal function in hypertensive type 2 diabetic patients with overt nephropathy-a pilot study (2011)
  • Author(s): Kanaoka T, Tamura K, Moriya T, Tanaka K, Konno Y, Kondoh S, Toyoda M, Umezono T, Fujikawa T, Ohsawa M, Dejima T, Maeda A, Wakui H, Haku S, Yanagi M, Mitsuhashi H, Ozawa M, Okano Y, Ogana N, Yamakawa T, Mizushima S, Suzuki D, Umemura S.
  • Journal Title: Clin Exp Hypertens Volume: 33 Pages: 255-263
  • Peer Reviewed
• [Journal Article] Involvement of Runx3 in the basal transcriptional activation of the mouse angiotensin II type 1 receptor-associated protein gene (2011)
  • Author(s): Matsuda M, Tamura K, Wakui H, Dejima T, Maeda A, Ohsawa M, Kanaoka T, Haku S, Azushima K, Yamasaki H, Saito D, Hirose T, Maeshima Y, Nagashima Y, Umemura S.
  • Journal Title: Physiol Genomics Volume: 43 Pages: 884-94
  • Peer Reviewed
• [Journal Article] Emerging concept of anti-hjrpertensive therapy based on ambulatory blood pressure profile in chronic kidney disease (2011)
  • Author(s): Hiromichi Wakui, et al
  • Journal Title: American Journal of Cardiovascular Disease Volume: 1 Pages: 236-243
  • Peer Reviewed
• [Journal Article] Prepubertal angiotensin blockade exerts long-term therapeutic effect through sustained ATRAP activation in salt-sensitive hypertensive rats (2011)
  • Author(s): Hiromichi Wakui, et al
  • Journal Title: Journal of Hypertension Volume: 29 Pages: 1919-1929
  • Peer Reviewed
• [Journal Article] Effects of multiple factorial intervention on ambulatory BP profile and renal function in hypertensive type 2 diabetic patients with overt nephropathy-a pilot study (2011)
  • Author(s): Hiromichi Wakui, et al
  • Journal Title: Clinical and Experimental Hypertension Volume: 33 Pages: 255-263
  • Peer Reviewed
• [Journal Article] Involvement of Runx3 in the basal transcriptional activation of the mouse angiotensin II type 1 receptor-associated protein gene (2011)
  • Author(s): Hiromichi Wakui, et al
  • Journal Title: Physiological Genomics Volume: 43 Pages: 884-894
  • Peer Reviewed
• [Journal Article] Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice (2010)
  • Author(s): Wakui H, Tamura K, Matsuda M, Bai Y, Dejima T, Shigenaga A, Masuda S, Azuma K, Maeda A, Hirose T, Ishigami T, Toya Y, Yabana M, Minamisawa S, Umemura S.
  • Journal Title: Am J Physiol Renal Physiol Volume: 299 Pages: 991-1003
  • Peer Reviewed
• [Journal Article] Expression of angiotensin II type 1 receptor-interacting molecule in normal human kidney and IgA nephropathy (2010)
  • Author(s): Masuda S, Tamura K, Wakui H, Maeda A, Dejima T, Hirose T, Toyoda M, Azuma K, Ohsawa M, Kanaoka T, Yanagi M, Yoshida S, Mitsuhashi H, Matsuda M, Ishigami T, Toya Y, Suzuki D, Nagashima Y, Umemura S.
  • Journal Title: Am J Physiol Renal Physiol Volume: 299 Pages: 720-31
  • Peer Reviewed
• [Journal Article] Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice (2010)
  • Author(s): Wakui H, Tamura K, Matsuda M, Bai Y, Dejima T, Shigenaga A, Masuda S, Azuma K, Maeda A, Hirose T, Ishigami T, Toya Y, Yabana M, Minamisawa S, Umemura S
  • Journal Title: American Journal of Physiology Renal Physiology Volume: 299
  • Peer Reviewed
• [Journal Article] Cardiac-specific activation of angiotensin II type 1 receptor-associated protein completely suppresses cardiac hypertrophy in chronic angiotensin II-infused mice. (2010)
  • Author(s): Wakui H, Tamura K, Tanaka Y, Matsuda M, Bai Y, Dejima T, Masuda S, Shigenaga A, Maeda A, Mogi M, Ichihara N, Kobayashi Y, Hirawa N, Ishigami T, Toya Y, Yabana M, Horiuchi M, Minamisawa S, Umemura S.
  • Journal Title: Hypertension Volume: 55 Pages: 1157-1164
  • Peer Reviewed
• [Presentation] 食塩感受性高血圧におけるアンジオテンシン受容体結合因子の病態生理学的意義について (2011)
  • Author(s): 涌井広道
  • Organizer: 第9回腎と高血圧Update
  • Place of Presentation: 品川プリンスホテル,東京
  • Year and Date: 2011-12-06
• [Presentation] Renal AT1 receptor-associated protein plays a role in the salt-sensitive blood pressure regulation (2011)
  • Author(s): 涌井広道
  • Organizer: The 4th International Aldosterone Forum in Japan
  • Place of Presentation: ロイヤルパークホテル東京,東京
  • Year and Date: 2011-05-14
• [Presentation] Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice (2011)
  • Author(s): 涌井広道
  • Organizer: 第16回アンジオテンシンカンファレンス
  • Place of Presentation: 東京
  • Year and Date: 2011-02-05
• [Presentation] Intrarenal suppression of angiotensin II type 1 receptor binding molecule in angiotensin II-infused mice (2010)
  • Author(s): 涌井広道
  • Organizer: Kidney frontier 2010
  • Place of Presentation: 第一ホテル東京,東京
  • Year and Date: 2010-12-18
• [Presentation] Cardiac-specific activation of angiotensin II type 1 receptor-associated protein completely suppresses cardiac hypertrophy in chronic angiotensin II-infused mice. (2010)
  • Author(s): 涌井広道
  • Organizer: 国際高血圧学会
  • Place of Presentation: バンクーバー、カナダ
  • Year and Date: 2010-09-30
• [Presentation] 慢性持続アンジオテンシンII投与により腎ATRAP発現量は減少する (2010)
  • Author(s): 涌井広道
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場,兵庫
• [Presentation] 尿細管特異的ATRAP発現量の増加は食塩感受性高血圧を抑制する (2010)
  • Author(s): 涌井広道
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場,兵庫
• [Remarks] 本研究成果により第9回腎と高血圧Update優秀賞受賞(平成23年12月)