The microRNA-15 family inhibits the TGFß-pathway in the heart.
Cardiovasc Res
; 104(1): 61-71, 2014 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-25103110
ABSTRACT
AIMS:
The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis, which contributes to the development of heart failure. Signalling via the TGFß-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 TGFß-pathway. METHODS ANDRESULTS:
We show that the miRNA-15 family, which we found to be up-regulated in the overloaded heart in multiple species, inhibits the TGFß-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 TGFß-pathway.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Transducción de Señal
/
Factor de Crecimiento Transformador beta
/
Cardiomegalia
/
Remodelación Ventricular
/
Miocitos Cardíacos
/
MicroARNs
/
Cardiomiopatías
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Idioma:
En
Revista:
Cardiovasc Res
Año:
2014
Tipo del documento:
Article
País de afiliación:
Países Bajos