| Project/Area Number |
15K07751
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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 |
Veterinary medical science
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| Research Institution | Rakuno Gakuen University (2016-2018)
Kitasato University (2015) |
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Principal Investigator |
Yasutomo Hori 酪農学園大学, 獣医学群, 准教授 (20406896)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 心不全 / 心臓線維化 / 交感神経受容体 / β3受容体 / 心臓線維芽細胞 |
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| Outline of Final Research Achievements |
There are α and β subtypes in adrenergic receptor (AR), and 3 subtypes in β-AR. Of these, the localization of β3-AR in the cardiovascular system has been clarified, and its pathological effects to the heart failure has been noted. In our study, the expression level of β3-AR in the left ventricle was extremely low, but the expression was confirmed in cardiac fibroblasts. In addition, β3-AR agonists increased the expression of the p44 / 42 MAPK (pERK1 / 2) and pCREB in cardiac fibroblasts, but β3-AR inhibitors significantly suppressed them. These results suggests that β3-AR transmits intracellular signals via ERK1 / 2 and CREB.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでに心臓線維芽細胞におけるβ3-ARの局在は知られておらず、β3交感神経受容体(AR)を介した心筋線維化のメカニズムは未知のままである。
本研究では、これまで知られていなかった心臓におけるβ3交感神経受容体(AR)の局在を明らかにし、心臓線維芽細胞における細胞シグナル経路の一端を解明することができた。これらのことはβ3-ARが心不全患者における心臓線維化の進行に関わっていることを示唆しており、β3-ARの抑制を介した心不全治療の可能性が期待される。今後は心臓線維芽細胞におけるβ3-ARとリモデリングに関する機能解析を行い、β3-ARと心臓線維化の関係を解明する必要がある。
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