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Functional Screenin...
Functional Screening Identifies MicroRNA Regulators of Corin Activity and Atrial Natriuretic Peptide Biogenesis
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- Celik, Selvi (författare)
- Lund University,Lunds universitet,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Karbalaei-Sadegh, Mardjaneh (författare)
- Lund University,Lunds universitet,Kardiologi,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Cardiology,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Rådegran, Göran (författare)
- Lund University,Lunds universitet,Lund Hemodynamic Lab,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital
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visa fler...
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- Smith, J. Gustav (författare)
- Lund University,Lunds universitet,Molecular Epidemiology and Cardiology,Forskargrupper vid Lunds universitet,Lund University Research Groups,Skåne University Hospital
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- Gidlöf, Olof (författare)
- Lund University,Lunds universitet,Molekylär kardiologi,Forskargrupper vid Lunds universitet,Molecular Cardiology,Lund University Research Groups
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visa färre...
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(creator_code:org_t)
- 2019
- 2019
- Engelska.
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Ingår i: Molecular and Cellular Biology. - 0270-7306. ; 39:23
- Relaterad länk:
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http://dx.doi.org/10... (free)
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visa fler...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Atrial natriuretic peptide (ANP) represents an attractive therapeutic target in hypertension and heart failure. The biologically active form of ANP is produced by the cardiac serine protease corin, and modulation of its activity might therefore represent a novel approach for ANP augmentation. MicroRNAs (miRNAs) are pervasive regulators of gene expression, but their potential role in regulating corin activity has not been elucidated. Our aim was to systematically identify and characterize miRNA regulators of corin activity in human cardiomyocytes. An assay for measuring serine protease activity in human induced pluripotent stem cell (iPS)-derived cardiomyocytes was used to perform a comprehensive screening of miRNA family inhibitors (n = 42). miRNA 1-3p (miR-1-3p) was identified as a potent inhibitor of corin activity. The interaction between miR-1-3p and a specific target site in the CORIN 3' untranslated region (3' UTR) was confirmed through argonaute 2 (AGO2)-RNA immunoprecipitation and reporter assays. Inhibition of miR-1-3p resulted in upregulation of CORIN gene and protein expression, as well as a concomitant increase in extracellular ANP. Additionally, miR-1-3p was found to interact with and inhibit the expression of several transcriptional activators of ANP gene expression. In conclusion, we have identified a novel regulator of corin activity and ANP biogenesis in human cardiomyocytes that might be of potential future therapeutic utility.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Nyckelord
- atrial natriuretic peptide
- cardiomyocyte
- corin
- heart failure
- microRNA
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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