期刊
MOLECULAR THERAPY-NUCLEIC ACIDS
卷 23, 期 -, 页码 968-981出版社
CELL PRESS
DOI: 10.1016/j.omtn.2021.01.015
关键词
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资金
- Sir Jules Thorn Trust
- Leverhulme Trust [RPG-2015-357]
- Medical Research Council [MRC MR/S036695/1]
- Biotechnology and Biological Sciences Research Council [BBSRC BB/T000805/1]
- International Juvenile Diabetes Research Foundation [JDRF 5-CDA-2014-225-A-N]
- SFI-DfE (NI) Investigator Award
- National Eye Research Centre [SAC 016]
- Queen's University Belfast Four Star Fund
- BBSRC [BB/T000805/1] Funding Source: UKRI
- MRC [MR/S036695/1] Funding Source: UKRI
miR-130a acts as a mediator in the hypoxic response of ECFCs, enhancing their angiogenic and vasoreparative abilities by coordinating the upregulation of VEGFR2/STAT3/HIF1 alpha axis through translational inhibition of Ddx6.
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% O-2, 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 HIF1 alpha via translational inhibition of Ddx6. These findings unveil a new role for miR-130a in hypoxia, whereby it activates the VEGFR2/STAT3/HIF1 alpha axis to enhance the vasoregenerative capacity of ECFCs.
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