Adrenomedullin/Cyclic AMP Pathway Induces Notch Activation and Differentiation of Arterial Endothelial Cells From Vascular Progenitors
| Autor: | Genta Narazaki, Hiroshi Itoh, Mina Hiraoka-Kanie, Toshiaki Ara, Jun K. Yamashita, Takami Yurugi-Kobayashi, Kazuwa Nakao, Takashi Nagasawa, Fumiyo Kita, Kentoku Yanagi, Emi Inoue, Shin-Ichi Nishikawa, Ursula Just, Akiko Nakano, Timm Schroeder |
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| Rok vydání: | 2006 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Endothelium Angiogenesis Cellular differentiation 8-Bromo Cyclic Adenosine Monophosphate Biology Cell Line Veins Adrenomedullin Mice chemistry.chemical_compound Internal medicine Cyclic AMP medicine Animals Progenitor cell Receptors Notch Stem Cells Endothelial Cells Cell Differentiation Drug Synergism Arteries Cell biology Vascular endothelial growth factor Endothelial stem cell Endocrinology medicine.anatomical_structure chemistry angiogenesis developmental biology embryonic stem cells endothelium vascular biology Stem cell Peptides Cardiology and Cardiovascular Medicine Signal Transduction |
| Zdroj: | Arterioscler. Thromb. Vasc. Biol. 26, 1977-1984 (2006) |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000234978.10658.41 |
| Popis: | Objective— The acquisition of arterial or venous identity is highlighted in vascular development. Previously, we have reported an embryonic stem (ES) cell differentiation system that exhibits early vascular development using vascular endothelial growth factor (VEGF) receptor-2 (VEGFR2)-positive cells as common vascular progenitors. In this study, we constructively induced differentiation of arterial and venous endothelial cells (ECs) in vitro to elucidate molecular mechanisms of arterial-venous specification. Methods and Results— ECs were induced from VEGFR2 + progenitor cells with various conditions. VEGF was essential to induce ECs. Addition of 8bromo-cAMP or adrenomedullin (AM), an endogenous ligand-elevating cAMP, enhanced VEGF-induced EC differentiation. Whereas VEGF alone mainly induced venous ECs, 8bromo-cAMP (or AM) with VEGF supported substantial induction of arterial ECs. Stimulation of cAMP pathway induced Notch signal activation in ECs. The arterializing effect of VEGF and cAMP was abolished in recombination recognition sequence binding protein at the Jκ site deficient ES cells lacking Notch signal activation or in ES cells treated with γ-secretase inhibitor. Nevertheless, forced Notch activation by the constitutively active Notch1 alone did not induce arterial ECs. Conclusions— Adrenomedullin/cAMP is a novel signaling pathway to activate Notch signaling in differentiating ECs. Coordinated signaling of VEGF, Notch, and cAMP is required to induce arterial ECs from vascular progenitors. |
| Databáze: | OpenAIRE |
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