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    MicroRNA410 Inhibits Pulmonary Vascular Remodeling via Regulation of Nicotinamide Phosphoribosyltransferase

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    Author
    Gao, Hui
    Song, Yang
    Machado, Roberto F.
    Date
    2019-07-09
    Journal
    Scientific Reports
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://www.doi.org/10.1038/s41598-019-46352-z
    Abstract
    Nicotinamide phosphoribosyltransferase (NAMPT) upregulation in human pulmonary artery endothelial cells (hPAECs) is associated with pulmonary arterial hypertension (PAH) progression and pulmonary vascular remodeling. The underlying mechanisms regulating NAMPT expression are still not clear. In this study, we aimed to study the regulation of NAMPT expression by microRNA410 (miR410) in hPAECs and explore the role of miR410 in the pathogenesis of experimental pulmonary hypertension. We show that miR410 targets the 3′ UTR of NAMPT and that, concomitant with NAMPT upregulation, miR410 is downregulated in lungs of mice exposed to hypoxia-induced pulmonary hypertension (HPH). Our results also demonstrate that miR410 directly inhibits NAMPT expression. Overexpression of miR410 in hPAECs inhibits basal and VEGF-induced proliferation, migration and promotes apoptosis of hPAECs, while miR410 inhibition via antagomirs has the opposite effect. Finally, administration of miR410 mimics in vivo attenuated induction of NAMPT in PAECs and prevented the development of HPH in mice. Our results highlight the role of miR410 in the regulation of NAMPT expression in hPAECs and show that miR410 plays a potential role in PAH pathobiology by targeting a modulator of pulmonary vascular remodeling. © 2019, The Author(s).
    Sponsors
    This study was funded by the National Heart, Lung, and Blood Institute (NHLBI) grant number R01HL111656, R01HL127342 and R01HL133951
    Keyword
    microRNA410
    pulmonary artery endothelial cells
    Vascular Remodeling
    Nicotinamide Phosphoribosyltransferase
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068752486&origin=inward; http://hdl.handle.net/10713/10107
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-019-46352-z
    Scopus Count
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    UMB Open Access Articles 2019

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