Cardiovascular research · 2014
The microRNA-15 family inhibits the TGFβ-pathway in the heart.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Tijsen Anke J, van der Made Ingeborg, van den Hoogenhof Maarten M, Wijnen Wino J, van Deel Elza D, de Groot Nina E, Alekseev Sergey, Fluiter Kees, Schroen Blanche, Goumans Marie-José, van der Velden Jolanda, Duncker Dirk J, Pinto Yigal M, Creemers Esther E
Аннотация
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.
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.
Предметные рубрики MeSH
3' Untranslated RegionsAnimalsCOS CellsCardiomegalyCardiomyopathiesCase-Control StudiesChlorocebus aethiopsDisease Models, AnimalFibrosisHep G2 CellsHumansMice, Inbred C57BLMicroRNAsMyocytes, CardiacProtein Serine-Threonine KinasesRats, TransgenicReceptor, Transforming Growth Factor-beta Type IReceptors, Transforming Growth Factor betaSignal TransductionSmad3 ProteinSmad7 ProteinTransfectionTransforming Growth Factor betaUp-RegulationVentricular Remodelingp38 Mitogen-Activated Protein Kinases