Role of KCa channels in preosteoblast proliferation
| Project/Area Number |
18K14929
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | Nagoya City University |
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Principal Investigator |
Kito Hiroaki 名古屋市立大学, 医薬学総合研究院(医学), 助教 (40749181)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 骨芽細胞 / カルシウム活性化カリウムチャネル / 細胞増殖 / VDR / カリウムチャネル / 細胞分化 / KCa3.1 / Kir2.1 / 前骨芽細胞 / イオンチャネル / 内向き整流性カリウムチャネル |
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| Outline of Final Research Achievements |
In present study, we showed that KCa3.1 were functionally expressed in mouse preosteoblast MC3T3-E1, and the activation of KCa3.1 promoted the cell growth of MC3T3-E1 cells. To clarify the physiological function of KCa3.1 in MC3T3-E1 cells, contribution of KCa3.1 to VDR agonists-induced suppression of cell proliferation were examined. Treatments with VDR agonists markedly decreased the expression levels of KCa3.1 transcripts and proteins in MC3T3-E1 cells. Treatments with VDR agonists also significantly decreased the expression of several transcriptional regulators of KCa3.1 such as histone deacetylase 2 (HDAC2) and Fra-1 composed of activation protein 1. Our results suggest that KCa3.1 is a new downstream target of VDR signaling and the down-regulation of KCa3.1 through the transcriptional repression of KCa3.1 contribute, at least partly, to the antiproliferative effects of VDR agonists in mouse pre-osteoblasts.
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| Academic Significance and Societal Importance of the Research Achievements |
骨芽細胞におけるイオンチャネル研究は、ストア作動性Ca2+流入の構成分子であるOrai1/STIM1を介したCa2+シグナルが骨芽細胞分化を制御することが報告されたものの、Ca2+流入の調節因子としてK+チャネルに焦点を置いた研究はほとんど行われていない。また、Ca2+透過チャネルはユビキタスに発現するのに対して、組織ごとに多様な発現を示すK+チャネルを対象とした創薬研究は組織特異的な薬物治療の可能性を広げることが期待される。以上のことから、応募者は本研究課題が、骨代謝性疾患の新規治療薬の開発において、有益な情報を提供し得るものと考えている。
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Report
(4 results)
Research Products
(17 results)
