AT1 receptor binding protein activation strategy in the treatment of hypertension and related organ injury
Project/Area Number |
19K18010
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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Research Institution | Yokohama City University |
Principal Investigator |
KOBAYASHI Ryu 横浜市立大学, 医学部, 客員研究員 (60805612)
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Project Period (FY) |
2019-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 慢性腎臓病 / 高血圧 / レニン-アンジオテンシン系 / レニン・アンジオテンシン系 / 尿細管 |
Outline of Research at the Start |
本研究課題では高血圧モデル動物,発生工学的手法により作製した組織特異的ATRAP発現制御動物およびヒト組織を用いて,ATRAPの発現・活性調節異常と高血圧・高血圧関連臓器障害との関連について多面的に検討し,高血圧・高血圧関連臓器障害の発症・進展におけるATRAPの病態生理学的意義の解明,およびATRAPに着目した新規分子標的治療法の開発に向けた検討を行う.ヒト組織でのATRAP発現レベルと,高血圧および高血圧関連臓器障害の重症度と臨床指標との関連を検討することにより,その早期診断法や新規治療法の発見につながる可能性がある.
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Outline of Final Research Achievements |
We have previously shown that ATRAP (angiotensin II receptor; associated protein; Agtrap) interacts with AT1R (angiotensin II type 1 receptor) and promotes constitutive internalization of AT1R so as to inhibit hyperactivation of its downstream signaling. ATRAP deficiency in proximal tubules did not exacerbate angiotensin-dependent hypertension in vivo. The results indicate that renal proximal tubule ATRAP has a minor role in angiotensin-dependent hypertension in vivo.
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Academic Significance and Societal Importance of the Research Achievements |
腎尿細管で高発現しているATRAPの活性化を行うことで,高血圧治療及び慢性腎臓病などの腎疾患における新たな分子標的治療実現のための検討を行うことを目的とする.
特に慢性腎臓病については,現時点で特効薬がない疾患でありながら患者は増加の一途をたどっており,病態改善に寄与する治療が実現できれば,社会的意義は大きいと考える.
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Report
(3 results)
Research Products
(7 results)
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[Journal Article] Effects of ATRAP in Renal Proximal Tubules on Angiotensin‐Dependent Hypertension2019
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
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Journal Title
Journal of the American Heart Association
Volume: 8
Issue: 8
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Angiotensin II type 1 receptor-associated protein deficiency attenuates sirtuin1 expression in an immortalised human renal proximal tubule cell line2019
Author(s)
Yamaji T, Yamashita A, Wakui H, Azushima K, Uneda K, Fujikawa Y, Haku S, Kobayashi R, Ohki K, Haruhara K, Kinguchi S, Ishii T, Yamada T, Urate S, Suzuki T, Abe E, Tanaka S, Kamimura D, Ishigami T, Toya Y, Takahashi H, Tamura K.
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Journal Title
Scientific Reports
Volume: 9
Issue: 1
Pages: 16550-16550
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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