Roles of Cyclic Adenosine Monophosphate Signaling in Endothelial Cell Differentiation and Arterial-Venous Specification During Vascular Development

DOI Web Site 被引用文献10件 参考文献103件
  • Yamamizu Kohei
    Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences; Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University
  • Yamashita Jun K.
    Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences; Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University

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Cyclic adenosine monophosphate (cAMP) is an important second messenger mediating physiological functions, including metabolism, gene expression, cell growth and differentiation. Recently, we demonstrated novel roles of cAMP pathway in endothelial cell (EC) differentiation and arterial-venous specification using an embryonic stem cell differentiation system. These studies offered a concept that vascular formation is accomplished by a 2-layered mechanism: (1) a basal mechanism for common EC differentiation, whereby vascular endothelial growth factor (VEGF) signaling plays a central role in the basal mechanism, and (2) a vascular diversification mechanism working on the basis of common EC differentiation. Vascular diversification, such as artery and vein formation, can be only achieved by enacting specific machineries in the presence of the basal EC machinery. cAMP/protein kinase A signaling contributes to common EC differentiation through upregulation of the VEGF-A receptors, Flk1 and neuropilin1. On the other hand, cAMP can activate phosphatidylinositol-3 kinase, which induces an arterial fate in vascular progenitors via dual activation of Notch and β-catenin signaling as an arterial-specific machinery. cAMP signaling thus plays a pivotal role in both the basal and diversification machinery during vascular development. (Circ J 2011; 75: 253-260)<br>

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  • Circulation Journal

    Circulation Journal 75 (2), 253-260, 2011

    一般社団法人 日本循環器学会

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