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2021 年度 実績報告書

Molecular regulation of blood vessel size by endothelial cells-the role of Marcksl1.

研究課題

研究課題/領域番号 19K06651
研究機関国立研究開発法人理化学研究所

研究代表者

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)

研究期間 (年度) 2019-04-01 – 2022-03-31
キーワードEndothelial cell / Tubulogenesis / Actin cytoskeleton / Blebbing / Haemodynamic forces / Marcksl1
研究実績の概要

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.

  • 研究成果

    (4件)

すべて 2021

すべて 雑誌論文 (1件) (うち国際共著 1件、 査読あり 1件) 学会発表 (3件) (うち招待講演 2件)

  • [雑誌論文] Endothelial cell mechanics and blood flow forces in vascular morphogenesis2021

    • 著者名/発表者名
      Li-Kun Phng , Heinz-Georg Belting
    • 雑誌名

      Seminars in Cell and Developmental Biology

      巻: 120 ページ: 32-43

    • DOI

      10.1016/j.semcdb.2021.06.005

    • 査読あり / 国際共著
  • [学会発表] Endothelial cell mechanoresponse to haemodynamic forces during vascular tubulogenesis2021

    • 著者名/発表者名
      Li-Kun Phng
    • 学会等名
      Mathematical Mechanobiology, RIMS Workshop, University of Kyoto, Japan.
    • 招待講演
  • [学会発表] Role of endothelial cell mechanoresponse to haemodynamic forces in the regulation of vessel morphology2021

    • 著者名/発表者名
      Li-Kun Phng
    • 学会等名
      EMBO Workshop “Vascular Malformations: from fundamental biology to therapeutic opportunities”. Badalona, Spain.
  • [学会発表] Endothelial cell mechanoresponse to haemodynamic forces during vascular lumenization2021

    • 著者名/発表者名
      Li-Kun Phng
    • 学会等名
      Cell & Tissue Hydraulics Mini-symposium, Mechanobiology Institute, University of Singapore.
    • 招待講演

URL: 

公開日: 2022-12-28  

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