The microRNA-15 family inhibits the TGFβ-pathway in the heart
AJ Tijsen, I Van Der Made… - Cardiovascular …, 2014 - academic.oup.com
AJ Tijsen, I Van Der Made, MM van den Hoogenhof, WJ Wijnen, ED van Deel, NE De Groot…
Cardiovascular research, 2014•academic.oup.comAims The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis,
which contributes to the development of heart failure. Signalling via the TGFβ-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 TGFβ-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 TGFβ-pathway by targeting of TGFBR1 and …
which contributes to the development of heart failure. Signalling via the TGFβ-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 TGFβ-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 TGFβ-pathway by targeting of TGFBR1 and …
Aims
The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis, which contributes to the development of heart failure. Signalling via the TGFβ-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 TGFβ-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 TGFβ-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 TGFβ-pathway.
Oxford University Press