Pathophysiological significance of angiotensin receptor-binding protein in leucocytes and immune cells
Project/Area Number |
19K17575
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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 53020:Cardiology-related
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Research Institution | Yokohama City University |
Principal Investigator |
UNEDA Kazushi 横浜市立大学, 医学研究科, 客員研究員 (90780370)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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Keywords | レニン・アンジオテンシン系 / ATRAP / 1型アンジオテンシン受容体 / AT1受容体 / マクロファージ / 白血球 / 糖尿病 / レニンアンジオテンシン系 |
Outline of Research at the Start |
本研究では,「白血球・免疫細胞におけるATRAP発現調節異常が,生活習慣病関連臓器障害の発症・進展に関与し,白血球・免疫細胞でのATRAP(AT1 receptor-associated protein) の発現レベルの制御により生活習慣病関連臓器障害を改善できる」との仮説を検証するため,生活習慣病モデル動物,組織ATRAP発現制御動物およびヒト血液検体などを用いて,生活習慣病関連臓器障害の発症・進展における白血球・免疫細胞でのATRAPの病態生理学的意義を生体レベルで明らかにし,ATRAPに着目した新規分子標的治療開発に向けた多面的な基礎的知見を得ることを目指す.
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Outline of Final Research Achievements |
ATRAP deficient mice exhibited an exacerbation of streptozotocin-induced diabetic glomerular injury compared to wild-type control mice. These phenomena were accompanied by decreased expression of CD206, a marker of alternatively activated and tissue-reparative M2 macrophages, in the kidney tubulointerstitium. There were no significant differences in the expression levels of M2 macrophage-related genes and CD206 in IL-10– and TGF-b–incubated bone marrow–derived macrophages from wild-type mice and ATRAP deficient mice. Additionally, adoptive transfer of M2- polarized macrophages into diabetic ATRAP-knockout mice ameliorated the glomerular injury. These results indicates that ATRAP-M2 macrophages axis is a therapeutic target for diabetic kidney diseases.
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Academic Significance and Societal Importance of the Research Achievements |
糖尿病性腎症に対するレニン-アンジオテンシン(RA)系阻害の腎保護効果の新たなメカニズムとして,腎尿細管RA系の過剰な活性化が,マクロファージの極性変化を介して糸球体障害を増悪させるという腎尿細管-マクロファージー糸球体連関の存在を新たに示した。糖尿病性腎症において既存薬によるRA系の過度な抑制は,むしろ副作用が増えることことが報告されているため,RA系の生理的シグナルには悪影響を与えずに,臓器障害と関連したシグナルのみ選択的に抑制できるATRAP-M2マクロファージ軸が,糖尿病性腎症の新たな治療標的となる可能性がある。
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice2021
Author(s)
Urate Shingo、Wakui Hiromichi、Azushima Kengo、Yamaji Takahiro、Suzuki Toru、Abe Eriko、Tanaka Shohei、Taguchi Shinya、Tsukamoto Shunichiro、Kinguchi Sho、Uneda Kazushi、Kanaoka Tomohiko、Atobe Yoshitoshi、Funakoshi Kengo、Yamashita Akio、Tamura Kouichi
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Journal Title
International Journal of Molecular Sciences
Volume: 22
Issue: 22
Pages: 12432-12432
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of Rikkunshito treatment on renal fibrosis/inflammation and body weight reduction in a unilateral ureteral obstruction model in mice2020
Author(s)
Wakui H, Yamaji T, Azushima K, Uneda K, Haruhara K, Nakamura A, Ohki K, Kinguchi S, Kobayashi R, Urate S, Suzuki T, Kamimura D, Minegishi S, Ishigami T, Kanaoka T, Matsuo K, Miyazaki T, Fujikawa T, Yamashita A, Tamura K.
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 1782-1782
DOI
Related Report
Peer Reviewed / Open Access
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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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[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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[Presentation] 腎近位尿細管AT1受容体結合因子がアンジオテンシン依存性高血圧に及ぼす影響(Effects of AT1 Receptor-Associated Protein in Renal Proximal Tubules on Angiotensin II-Mediated Hypertension)2019
Author(s)
金口 翔, 涌井 広道, 小豆島 健護, 春原 浩太郎, 高口 知之, 大城 光二, 畝田 一司, 白 善雅, 山地 孝拡, 山田 貴之, 小林 竜, 石上 友章, 山下 暁朗, 藤川 哲也, 田村 功一
Organizer
第42回日本高血圧学会総会
Related Report
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