MiR-130a activates the VEGFR2/STAT3/HIF1α axis to potentiate the vasoregenerative capacity of endothelial colony forming cells in hypoxia

Jasenka Guduric-Fuchs, Edoardo Pedrini, Judith Lechner, Sarah E.J. Chambers, Christina L. O'Neill, Joana Mendes Lopes de Melo, Varun Pathak, Rachel H. Church, Stuart McKeown, James Bojdo, Kiran J. McLoughlin, Alan W. Stitt, Reinhold J. Medina

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Abstract

Hypoxia modulates reparative angiogenesis, which is a tightly regulated pathophysiological process. MicroRNAs (miRNAs) are important regulators of gene expression in hypoxia and angiogenesis. However, we do not yet have a clear understanding of how hypoxia-induced miRNAs fine-tune vasoreparative processes. Here, we identify miR-130a as a mediator of the hypoxic response in human primary endothelial colony-forming cells (ECFCs), a well-characterized subtype of endothelial progenitors. Under hypoxic conditions of 1% O2, miR-130a gain-of-function enhances ECFC pro-angiogenic capacity in vitro and potentiates their vasoreparative properties in vivo. Mechanistically, miR-130a orchestrates upregulation of VEGFR2, activation of STAT3, and accumulation of HIF1α via translational inhibition of Ddx6. These findings unveil a new role for miR-130a in hypoxia, whereby it activates the VEGFR2/STAT3/HIF1α axis to enhance the vasoregenerative capacity of ECFCs.
Original languageEnglish
Pages (from-to)968-981
JournalMolecular Therapy: Nucleic Acids
Volume23
Early online date20 Jan 2021
DOIs
Publication statusPublished - 05 Mar 2021

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