miR-1-5p targets TGF-βR1 and is suppressed in the hypertrophying hearts of rats with pulmonary arterial hypertension
Authors
Garfield, Benjamin E.
Crosby, Alexi
Morrell, Nick W.
Wort, Stephen J.
Kemp, Paul R.
Publication Date
2020-02-28Journal Title
PLOS ONE
Publisher
Public Library of Science
Volume
15
Issue
2
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Connolly, M., Garfield, B. E., Crosby, A., Morrell, N. W., Wort, S. J., & Kemp, P. R. (2020). miR-1-5p targets TGF-βR1 and is suppressed in the hypertrophying hearts of rats with pulmonary arterial hypertension. PLOS ONE, 15 (2) https://doi.org/10.1371/journal.pone.0229409
Abstract
The microRNA miR-1 is an important regulator of muscle phenotype including cardiac muscle. Down-regulation of miR-1 has been shown to occur in left ventricular hypertrophy but its contribution to right ventricular hypertrophy in pulmonary arterial hypertension are not known. Previous studies have suggested that miR-1 may suppress transforming growth factor-beta (TGF-β) signalling, an important pro-hypertrophic pathway but only indirect mechanisms of regulation have been identified. We identified the TGF-β type 1 receptor (TGF-βR1) as a putative miR-1 target. We therefore hypothesized that miR-1 and TGF-βR1 expression would be inversely correlated in hypertrophying right ventricle of rats with pulmonary arterial hypertension and that miR-1 would inhibit TGF-β signalling by targeting TGF-βR1 expression. Quantification of miR-1 and TGF-βR1 in rats treated with monocrotaline to induce pulmonary arterial hypertension showed appropriate changes in miR-1 and TGF-βR1 expression in the hypertrophying right ventricle. A miR-1-mimic reduced enhanced green fluorescent protein expression from a reporter vector containing the TGF-βR1 3’- untranslated region and knocked down endogenous TGF-βR1. Lastly, miR-1 reduced TGF-β activation of a (mothers against decapentaplegic homolog) SMAD2/3-dependent reporter. Taken together, these data suggest that miR-1 targets TGF-βR1 and reduces TGF-β signalling, so a reduction in miR-1 expression may increase TGF-β signalling and contribute to cardiac hypertrophy.
Keywords
Research Article, Biology and life sciences, Research and analysis methods, Medicine and health sciences
Sponsorship
British Heart Foundation (FS/14/71/31038)
Identifiers
pone-d-19-27153
External DOI: https://doi.org/10.1371/journal.pone.0229409
This record's URL: https://www.repository.cam.ac.uk/handle/1810/302891
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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