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Olof Gidlöf

Research project participant

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Functional Screening Identifies MicroRNA Regulators of Corin Activity and Atrial Natriuretic Peptide Biogenesis

Author

  • Selvi Celik
  • Mardjaneh Karbalaei-Sadegh
  • Göran Rådegran
  • J. Gustav Smith
  • Olof Gidlöf

Summary, in English

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.

Department/s

  • Molecular Epidemiology and Cardiology
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Cardiology
  • Lund Hemodynamic Lab
  • EpiHealth: Epidemiology for Health
  • Molecular Cardiology

Publishing year

2019-12

Language

English

Publication/Series

Molecular and Cellular Biology

Volume

39

Issue

23

Document type

Journal article

Publisher

American Society for Microbiology

Topic

  • Cell and Molecular Biology
  • Cardiac and Cardiovascular Systems

Keywords

  • atrial natriuretic peptide
  • cardiomyocyte
  • corin
  • heart failure
  • microRNA

Status

Published

Research group

  • Molecular Epidemiology and Cardiology
  • Lund Hemodynamic Lab
  • Molecular Cardiology

ISBN/ISSN/Other

  • ISSN: 0270-7306