The implication of ATP2B1 gene in blood pressure regulation and Ca homeostasis
| Project/Area Number |
16K09648
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
Hirawa Nobuhito 横浜市立大学, 附属市民総合医療センター, 准教授 (20315766)
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| Co-Investigator(Kenkyū-buntansha) |
谷津 圭介 横浜市立大学, 医学研究科, 客員研究員 (10457856)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | ATP2B1 / 高血圧 / カルシウムチャネル / 副甲状腺ホルモン / Ca拮抗薬 / Ca代謝 / 一酸化窒素 / カルシウム / ノックアウト / 降圧メカニズム / トランスジェニック / 血管収縮 |
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| Outline of Final Research Achievements |
The ATP2B1 gene is associated with hypertension. The ATP2B1 gene encodes plasma membrane calcium ATPase 1 (PMCA1), which has been thought to regulate only intracellular Ca(2+) concentration. We examined the alterations of calcium related factors in systemic heater ATP2B1 knock-out [ATP2B1(+/-)] mice. ATP2B1(+/-) mice exhibited hypocalcemia. The expression of ATP2B1 in the kidney and small intestine decreased, and hypercalciuria was confirmed in ATP2B1(+/-) mice. The intact-PTH levels were lower, and bone mineral density was increased in these mice. These results suggest that hypocalcemia is mainly a result of inhibited bone resorption without compensation by PTH secretion in the case of ATP2B1 knockout. Moreover, NO production may be affected by reduced PTH secretion, which may cause the increase in vascular contractility in these mice. The ATP2B1 gene is important for not only intra-cellular calcium regulation but also for calcium homeostasis and blood pressure control.
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| Academic Significance and Societal Importance of the Research Achievements |
高血圧は、脳心血管病の最大のリスク因子である。中壮年者の血圧を120/80mmHg未満にコントロールされれば、脳心血管病の死亡は、60%抑制することができると考えられている。このような国民病である高血圧を制圧することができれば、国民が元気に長生きできる可能性が高まる。そこで、本研究では、高血圧を制圧するために、血圧の上昇するメカニズム、最適な降圧治療を明らかにするために、高血圧関連遺伝子ATP2B1の意義を明らかにした。本遺伝子は血管の収縮性に関連することが明らかとなり、降圧治療のテーラーメイド医療に有用であることが示唆された。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] The effects of anti-hypertensive drugs and the mechanism of hypertension in vascular smooth muscle cell-specific ATP2B1 knockout mice.2018
Author(s)
Okuyama Y, Hirawa N, Fujita M, Fujiwara A, Ehara Y, Yatsu K, Sumida K, Kagimoto M, Katsumata M, Kobayashi Y, Saka S, Umemura S, Tamura K.
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Journal Title
Hypertens Res.
Volume: 41(2)
Issue: 2
Pages: 80-87
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Calcium metabolism in systemic heterozygous ATP2B1-null mice2017
Author(s)
Yosuke Ehara, Nobuhito Hirawa, Kouichiro Sumida, Minako Kagimoto, Yuki Ooki, Megumi Fujita, Mari Katumata, Akira Fujiwara, Yusuke Kobayashi, Sanae Saka, Ikuma Katou, Keisuke Yatsu, Satoshi Umemura, and Kouichi Tamura
Organizer
American Society of Nephrology Kidney Week 2017 Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Decreased blood pressure in vascular smooth muscle specific ATP2B1 overexpressing mice2017
Author(s)
Yosuke Ehara, Nobuhito Hirawa, Kouichiro Sumida, Minako Kagimoto, Yuki Ooki, Megumi Fujita, Mari Katumata, Akira Fujiwara, Yusuke Kobayashi, Sanae Saka, Ikuma Katou, Keisuke Yatsu, Satoshi Umemura, and Kouichi Tamura
Organizer
American Society of Nephrology Kidney Week 2017 Annual Meeting
Related Report
Int'l Joint Research
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