2021 Fiscal Year Final Research Report
Molecular regulation of blood vessel size by endothelial cells-the role of Marcksl1.
| Project/Area Number |
19K06651
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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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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Phng Li Kun 国立研究開発法人理化学研究所, 生命機能科学研究センター, チームリーダー (70794098)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | Endothelial cell / Blood vessels / Morphogenesis / Lumen / Mechanobiology / Actin / Marcksl1 / Bleb |
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| Outline of Final Research Achievements |
The efficient distribution gases and solutes to tissues is facilitated by blood flow pumped through blood vessels. The formation and maintenance of vascular tubes are therefore critical for growth and tissue physiology. In this study, we identified a role of the actin-binding protein, Marcksl1, in modulating the mechanical properties of endothelial cell (EC) to regulate cell shape and vessel structure. Increasing and depleting Marcksl1 expression level results in an increase and decrease, respectively, in EC size and vessel diameter. Furthermore, overexpression of Marcksl1 induces ectopic membrane blebbing that is suppressed by reduced blood flow. Detailed analysis reveals that Marcksl1 promotes the formation of linear actin bundles and decreases actin density at the EC cortex. Our findings reveal that a balanced network of linear and branched actin at the EC cortex is essential for conferring resistance to the deforming forces of blood flow and pressure to regulate vessel structure.
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| Free Research Field |
Vascular development
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| Academic Significance and Societal Importance of the Research Achievements |
Vascular diseases such as cerebral carvenous malformation and aneurysms are characterized by abnormal vessel structure that are prone to rupture and can lead to death. Findings from our study contribute to the understanding of how vascular malformations arise and lead to the development of therapy.
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