microRNA-133a attenuates cardiomyocyte hypertrophy by targeting PKCδ and Gq

Mol Cell Biochem. 2018 Feb;439(1-2):105-115. doi: 10.1007/s11010-017-3140-8. Epub 2017 Aug 9.

Abstract

During the past decade, microRNAs have continuously been suggested as a promising therapeutic tool due to their beneficial effects, such as their multi-targets and multi-functions in pathologic conditions. As a pathologic phenotype is generally regulated by multiple signaling pathways, in this study we identified a microRNA regulating multiple target genes within cardiac hypertrophic signaling pathways. microRNA-133a is known to play a crucial role in cardiac hypertrophy. However, the role of microRNA-133a, which may regulate several signaling pathways in norepinephrine-induced cardiac hypertrophy via multi-targeting, has not been investigated. In the current study, we showed that microRNA-133a can protect cardiomyocyte hypertrophy against norepinephrine stimulation in neonatal rat ventricular cardiomyocytes via new targets, PKCδ and Gq, all of which are related to downstream signaling pathways of the α1-adrenergic receptor. Taken together, these results suggest the advantages of the therapeutic use of microRNAs as an effective potential drug regulating multiple signaling pathways under pathologic conditions.

Keywords: Cardiomyocyte hypertrophy; Gq; Norepinephrine; PKCδ; microRNA-133a.

MeSH terms

  • Animals
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism*
  • MicroRNAs / metabolism*
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Protein Kinase C-delta / metabolism*
  • Rats
  • Receptor, Adenosine A1 / metabolism
  • Signal Transduction*

Substances

  • MIRN133 microRNA, rat
  • MicroRNAs
  • Receptor, Adenosine A1
  • Prkcd protein, rat
  • Protein Kinase C-delta
  • GTP-Binding Protein alpha Subunits, Gq-G11