The microRNA-15 family inhibits the TGF beta-pathway in the heart

Anke J. Tijsen, Ingeborg van der Made, Maarten M. van den Hoogenhof, Wino J. Wijnen, Elza D. van Deel, Nina E. de Groot, Sergey Alekseev, Kees Fluiter, Blanche Schroen, Marie-Jose Goumans, Jolanda van der Velden, Dirk J. Duncker, Yigal M. Pinto, Esther E. Creemers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

125 Citations (Web of Science)

Abstract

Aims The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis, which contributes to the development of heart failure. Signalling via the TGF beta-pathway is crucial for this remodelling. Here we tested the hypothesis that microRNAs in the overloaded heart regulate this remodelling process via inhibition of the TGFb-pathway. Methods and results We show that the miRNA-15 family, which we found to be up-regulated in the overloaded heart in multiple species, inhibits the TGFb-pathway by targeting of TGFBR1 and several other genes within this pathway directly or indirectly, including p38, SMAD3, SMAD7, and endoglin. Inhibition of miR-15b by subcutaneous injections of LNA-based antimiRs in C57BL/6 mice subjected to transverse aorta constriction aggravated fibrosis and to a lesser extent also hypertrophy. Conclusion We identified the miR-15 family as a novel regulator of cardiac hypertrophy and fibrosis acting by inhibition of the TGF beta-pathway.
Original languageEnglish
Pages (from-to)61-71
JournalCardiovascular Research
Volume104
Issue number1
DOIs
Publication statusPublished - 1 Oct 2014

Keywords

  • Fibrosis
  • Hypertrophy
  • miRNA-15 family
  • TGF beta-pathway

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