Hypoxia-Induced Arterial Differentiation Requires Adrenomedullin and Notch Signaling

Lee, Kian Leong (author)

Ortega, German C. (author)

Sohl, Marcus (author)

Li, Xiujuan (author): Uppsala universitet,Cancer och vaskulärbiologi,Rudbeck Laboratory

Claesson-Welsh, Lena (author): Uppsala universitet,Cancer och vaskulärbiologi,Rudbeck Laboratory

(creator_code:org_t)

Mary Ann Liebert Inc, 2013
2013
English.
In: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 22:9, s. 1360-1369

Related links:: https://urn.kb.se/re...; show more...; https://doi.org/10.1...; http://kipublication...; show less...

Abstract Subject headings

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.

By the author/editor: Lanner, Fredrik; Lee, Kian Leong; Ortega, German C ...; Sohl, Marcus; Li, Xiujuan; Jin, Shaobo; show more...; Hansson, Emil M.; Claesson-Welsh, ...; Poellinger, Lore ...; Lendahl, Urban; Farnebo, Filip; show less...

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