2021 Fiscal Year Annual Research Report
Molecular regulation of blood vessel size by endothelial cells-the role of Marcksl1.
| Project/Area Number |
19K06651
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Phng LiKun 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 / Tubulogenesis / Actin cytoskeleton / Blebbing / Haemodynamic forces / Marcksl1 |
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| Outline of Annual Research Achievements |
The efficient distribution and exchange of gases and solutes to cells and tissues at distal portions of the body are facilitated by tubular organs. In vertebrates, oxygen and metabolites are distributed throughout the body by blood flow pumped through vascular tubes. Endothelial cells (ECs) line the innermost surface of the vessels and are subjected to the mechanical forces of blood flow such as blood pressure and wall shear stress. In this study, we discovered that ECs use the actin cytoskeleton to regulate its shape and vessel structure when they are exposed to blood pressure during lumen formation. By using zebrafish as an animal model, we demonstrated that ECs respond to blood pressure by generating a balanced network of linear and branched actin bundles in its cortex. When we genetically and pharmacologically increased the formation of linear actin bundles in ECs, excessive membrane blebbing (spherical membrane protrusions) and enlarged ECs were induced, leading to abnormally dilated vessels. Our findings therefore highlight the importance of ECs to mechanically resist the deforming forces of blood pressure to regulate blood vessel architecture.
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