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

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 pro...

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Bibliographic Details
Published in:Molecular therapy. Nucleic acids 2021-03, Vol.23, p.968-981
Main Authors: Guduric-Fuchs, Jasenka, Pedrini, Edoardo, Lechner, Judith, Chambers, Sarah E.J., O’Neill, Christina L., Mendes Lopes de Melo, Joana, Pathak, Varun, Church, Rachel H., McKeown, Stuart, Bojdo, James, Mcloughlin, Kiran J., Stitt, Alan W., Medina, Reinhold J.
Format: Article
Language:English
Subjects:
angiogenesis
ECFC
endothelial
endothelial cell
endothelial progenitor
endothelium
hypoxia
miRNA
Original
vascular repair
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Summary: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. [Display omitted] Cell therapies are often delivered into hypoxic tissues, which limits cell survival and engraftment. Guduric-Fuchs et al. demonstrate that miR-130a, enhanced endothelial colony-forming cells (ECFCs) function under hypoxia via activation of the VEGFR2/STAT3/HIF1α axis. miR-130a modulation in ECFCs offers an effective strategy to enhance their vasoreparative properties under hypoxia.
ISSN:2162-2531
2162-2531
DOI:10.1016/j.omtn.2021.01.015