2022 Fiscal Year Final Research Report
Involvement of inter-organelle Ca2+ network in developement of deseases caused by smooth muscle remoedeling
| Project/Area Number |
19H03381
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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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 |
Suzuki Yoshiaki 名古屋市立大学, 医薬学総合研究院(薬学), 講師 (80707555)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | カルシウムシグナル / 血管平滑筋 / カベオリン / ミトフュージン / ジャンクトフィリン / CaMKK2 / 血管リモデリング / マクロファージ |
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| Outline of Final Research Achievements |
Ca2+ is involved in various biological processes such as cell proliferation, differentiation, and cell death. Ca2+ channels and their downstream molecules form Ca2+ microdomains to form stimulus-specific signaling. Vascular smooth muscle cells (VSMCs) form the tunica media of blood vessels and regulate blood flow by changing the diameter of blood vessels. The identity and significance of Ca2+ microdomains in VSMCs remain largely unknown. In this study, we clarified that scaffolding proteins such as caveolin-1, junctophilin-2, and mitofusin-2 accumulate signal molecules to form Ca2+ microdomains, and are involved in vascular tension, cell proliferation, and remodeling.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
VSMCはCa2+シグナルを介した収縮・弛緩により血管径を制御し、全身の血流を適切に維持する。一方、VSMCの異常は高血圧や動脈硬化などの血管リモデリング疾患につながる。我々は、①caveolin-1やjunctophilin-2がCa2+濃度や収縮性を制御する機構、②mitofusin-2がCa2+シグナルを介したATP産生と細胞増殖を引き起こす機構、③caveolin-1がCa2+シグナルを炎症性の遺伝子に変換して血管リモデリングを誘発する機構を発見した。本研究成果は、VSMCによる血流制御機構の理解と血管リモデリング疾患の発症機序の解明およびその治療法の創出に結びつくと期待される。
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