dc.contributor.author | Scrimgeour, Nathan Robert | |
dc.contributor.author | Wrobel, Aleksandra Zofia | |
dc.contributor.author | Pinho, Maria | |
dc.contributor.author | Høydal, Morten | |
dc.date.accessioned | 2021-09-20T07:30:58Z | |
dc.date.available | 2021-09-20T07:30:58Z | |
dc.date.created | 2019-12-13T12:45:09Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0363-6143 | |
dc.identifier.uri | https://hdl.handle.net/11250/2779021 | |
dc.description.abstract | Matrix metalloproteinases (MMP) are important for cardiac remodeling. Recently, microRNA (miR)-451a has been found to inhibit the expression of both MMP-2 and MMP-9 in human malignancies, but its role in cardiomyocytes has not been explored. We hypothesized that miR-451a modulates MMP-2 and MMP-9 levels in human cardiomyocytes. The role of miR-451a on regulation of MMP-2 and MMP-9 was evaluated in two separate pathological models using Cor.4U human inducible pluripotent stem cell-derived cardiomyocytes (hiPS-CMs): 1) endothelin-1 (ET-1), and 2) 48-h hypoxia (1% O2). Both models were transfected with synthetic miR-451a mimics or scramble control. Expression of both mRNA and miR was determined by quantitative real-time polymerase chain reaction and protein activity by (MMP-2/9) activity assay. Bioinformatic analyses were performed using Targetscan 7.1 and STRING 10.5. hiPS-CMs stimulated by hypoxia increased both MMP-2 and MMP-9 expression levels compared with normoxia (P < 0.05), whereas ET-1 stimulation only increased the MMP-9 level compared with vehicle controls (P < 0.05). miR-451a mimics prevented the increase of MMP-2 and MMP-9 expression in both models. Protein activity of MMP-2 and MMP-9 was confirmed to be lower following treatment with miR-451a mimic compared with scramble-controls. Six of 28 predicted gene transcripts of miR-451a were linked to MMP-2 and MMP-9; Macrophage migration inhibitory factor (MIF) was the only predicted target of miR-451a that was increased by ET-1 and hypoxia and reduced following miR-451a mimic transfection. miR-451a prevent the increase of MMP-2 and MMP-9 in human cardiomyocytes during pathological stress. The modulation by miR-451a on MMP-2 and MMP-9 is caused by MIF. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | American Physiological Society | en_US |
dc.title | microRNA-451a prevents activation of matrix metalloproteinases 2 and 9 in human cardiomyocytes during pathological stress stimulation. | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.volume | 318 | en_US |
dc.source.journal | American Journal of Physiology - Cell Physiology | en_US |
dc.source.issue | 1 | en_US |
dc.identifier.doi | 10.1152/ajpcell.00204.2019 | |
dc.identifier.cristin | 1760531 | |
dc.description.localcode | This version of the article will not be available due to copyright restrictions (c) 2019 by American Physiological Society | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |