MicroRNA-21 and -146b are involved in the pathogenesis of murine viral myocarditis by regulating TH-17 differentiation

Arch Virol. 2013 Sep;158(9):1953-63. doi: 10.1007/s00705-013-1695-6. Epub 2013 Apr 16.

Abstract

Viral myocarditis (VMC) is a common cardiovascular disease, and microRNAs (miRNAs) have been postulated to be involved in its pathology. Using microarrays, we observed that miRNA-21 and -146b were upregulated in a murine model of VMC. We also found that miRNA-451 was downregulated. In vivo silencing of miRNA-21 and -146b resulted in less-severe VMC. Overexpression of miRNA-451 did not ameliorate the severity of VMC. Further work revealed that inhibition of miRNA-21 and -146b decreased the expression levels of Th17 and RORγt . Overexpression of miRNA-451 had no effect on IL-17 and RORγt expression. Inhibition of miRNA-21 and -146b might ameliorate myocardium inflammation by mediating downregulation of RORγt expression, indicating that these miRNAs are involved in the pathogenesis of murine VMC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Line
  • Coxsackievirus Infections* / genetics
  • Coxsackievirus Infections* / physiopathology
  • Coxsackievirus Infections* / virology
  • Disease Models, Animal
  • Enterovirus B, Human / pathogenicity*
  • Gene Expression Profiling
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology*
  • Myocarditis* / genetics
  • Myocarditis* / physiopathology
  • Myocarditis* / virology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Oligonucleotide Array Sequence Analysis
  • Th17 Cells / cytology*
  • Up-Regulation

Substances

  • MIRN146 microRNA, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Rorc protein, mouse