Activation of the skin renin-angiotensin system contributes to the development of hypertension
| Project/Area Number |
20K21606
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 53:Organ-based internal medicine and related fields
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| Research Institution | Yokohama City University |
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Principal Investigator |
TAMURA Kouichi 横浜市立大学, 医学研究科, 教授 (40285143)
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| Project Period (FY) |
2020-07-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 情報伝達系 / 受容体 / 腎臓病・高血圧 / 病態解明 / 治療標的 / 臓器連関 / 皮膚 / 循環調節 / 血圧 |
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| Outline of Research at the Start |
本研究では、外的環境に対する防御機能を担う皮膚組織について、「腎臓組織と共通の構造上の特徴を有し、RAA系構成要素遺伝子の発現が認められる」こと、「心血管腎臓病(病態連関病)の惹起物質(アンジオテンシンII)に対する受容体(AT1受容体)への新規結合蛋白であり受容体機能選択的制御作用を特長とする因子(ATRAP)の発現が認められる」ことに着目する。そして、(1) 皮膚組織ATRAPと血圧を中心とした循環系調節機構との関連性を明らかにし、(2) 皮膚組織ATRAPが皮膚組織と心血管組織・腎組織との新たな臓器連関における『鍵因子』として“心血管腎臓病(病態連関病)”の治療標的となり得ることを示す。
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| Outline of Final Research Achievements |
Recent studies suggests that modulation of vascular function and Na+ storage in the skin may contribute to blood pressure regulation in physiology and pathophysiology. Although the renin-angiotensin system, one of principal blood pressure regulators, reportedly exists in the skin tissue, its functional role remains unclear. This study aims to examine a putative role of skin tissue renin-angiotensin system in blood pressure regulation by animal experiments using genetic engineered mice and by clinical experiments using human skin samples. The results of our study suggest that functional status of skin renin-angiotensin system activity may exert a modulatory effect on blood pressure in response to certain pathological stimuli.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、外的環境に対する防御機能を担う皮膚組織に存在する循環制御メカニズムの皮膚組織レニン-アンジオテンシン系の意義に着目し、臓器間ネットワーク制御による高血圧克服のための治療標的としての意義を明らかにし、また、皮膚組織と高血圧との新たな接点を提唱することができた。今後は皮膚組織レニン-アンジオテンシン系が、高血圧などの予防・治療法開発の新規標的となる可能性がある。
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Right ventricular overloading is attenuated in monocrotaline-induced pulmonary hypertension model rats with a disrupted Gpr143 gene, the gene that encodes the 3,4-l-dihydroxyphenyalanine (l-DOPA) receptor.2022
Author(s)
Nakano M, Koga M, Hashimoto T, Matsushita N, Masukawa D, Mizuno Y, Uchimura H, Niikura R, Miyazaki T, Nakamura F, Zou S, Shimizu T, Saito M, Tamura K, Goto T, Goshima Y.
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Journal Title
J Pharmacol Sci.
Volume: 148
Issue: 2
Pages: 214-220
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic impact of muscle and fat mass in patients with heart failure.2021
Author(s)
Konishi M, Akiyama E, Matsuzawa Y, Sato R, Kikuchi S, Nakahashi H, Maejima N, Iwahashi N, Kosuge M, Ebina T, Hibi K, Misumi T, von Haehling S, Anker SD, Tamura K, Kimura K.
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Journal Title
J Cachexia Sarcopenia Muscle.
Volume: 12
Issue: 3
Pages: 568-576
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Association of the ratio of visceral-to-subcutaneous fat volume with renal function among patients with primary aldosteronism.2021
Author(s)
Haze T, Hatakeyama M, Komiya S, Kawano R, Ohki Y, Suzuki S, Kobayashi Y, Fujiwara A, Saka S, Tamura K, Hirawa N.
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Journal Title
Hypertens Res.
Volume: 44
Issue: 10
Pages: 1341-1351
DOI
Related Report
Peer Reviewed
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[Journal Article] Association of aldosterone and blood pressure with the risk for cardiovascular events after treatments in primary aldosteronism.2021
Author(s)
1.Haze T, Hirawa N, Yano Y, Tamura K, Kurihara I, Kobayashi H, Tsuiki M, Ichijo T, Wada N, Katabami T, Yamamoto K, Oki K, Inagaki N, Okamura S, Kai T, Izawa S, Yamada M, Chiba Y, Tanabe A, Naruse M.
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Journal Title
Atherosclerosis.
Volume: 324
Pages: 84-90
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Age-stratified comparison of clinical outcomes between medical and surgical treatments in patients with unilateral primary aldosteronism.2021
Author(s)
2.Nakamaru R, Yamamoto K, Akasaka H, Rakugi H, Kurihara I, Yoneda T, Ichijo T, Katabami T, Tsuiki M, Wada N, Yamada T, Kobayashi H, Tamura K, Ogawa Y, Kawashima J, Inagaki N, Fujita M, Watanabe M, Kamemura K, Okamura S, Tanabe A, Naruse M; JPAS/JRAS Study Group.
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Journal Title
Sci Rep.
Volume: 11
Issue: 1
Pages: 6925-6925
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Associations Between Changes in Plasma Renin Activity and Aldosterone Concentrations and Changes in Kidney Function After Treatment for Primary Aldosteronism.2020
Author(s)
19.Kobayashi Y, Haze T, Yano Y, Tamura K, Kurihara I, Ichijo T, Yoneda T, Katabami T, Tsuiki M, Wada N, Ogawa Y, Kawashima J, Sone M, Inagaki N, Yamada T, Okamoto R, Fujita M, Kamemura K, Yamamoto K, Izawa S, Tanabe A, Naruse M; JPAS/JRAS Study Group.
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Journal Title
Kidney Int Rep.
Volume: 5
Issue: 8
Pages: 1291-1297
DOI
Related Report
Peer Reviewed / Open Access
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