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Hypoxia-Induced Arterial Differentiation Requires Adrenomedullin and Notch Signaling
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2013 (Engelska)Ingår i: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 22, nr 9, s. 1360-1369Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Hypoxia (low oxygen) and Notch signaling are 2 important regulators of vascular development, but how they interact in controlling the choice between arterial and venous fates for endothelial cells during vasculogenesis is less well understood. In this report, we show that hypoxia and Notch signaling intersect in promotion of arterial differentiation. Hypoxia upregulated expression of the Notch ligand Dll4 and increased Notch signaling in a process requiring the vasoactive hormone adrenomedullin. Notch signaling also upregulated Dll4 expression, leading to a positive feedback loop sustaining Dll4 expression and Notch signaling. In addition, hypoxia-mediated upregulation of the arterial marker genes Depp, connexin40 (Gja5), Cxcr4, and Hey1 required Notch signaling. In conclusion, the data reveal an intricate interaction between hypoxia and Notch signaling in the control of endothelial cell differentiation, including a hypoxia/adrenomedullin/Dll4 axis that initiates Notch signaling and a requirement for Notch signaling to effectuate hypoxia-mediated induction of the arterial differentiation program.

Ort, förlag, år, upplaga, sidor
2013. Vol. 22, nr 9, s. 1360-1369
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-200680DOI: 10.1089/scd.2012.0259ISI: 000318153900005OAI: oai:DiVA.org:uu-200680DiVA, id: diva2:624786
Tillgänglig från: 2013-06-03 Skapad: 2013-06-03 Senast uppdaterad: 2017-12-06Bibliografiskt granskad

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Li, XiujuanClaesson-Welsh, Lena

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