Knock-out of MicroRNA 145 impairs cardiac fibroblast function and wound healing post-myocardial infarction.
J Cell Mol Med
; 24(16): 9409-9419, 2020 08.
Article
en En
| MEDLINE
| ID: mdl-32628810
ABSTRACT
Prevention of infarct scar thinning and dilatation and stimulation of scar contracture can prevent progressive heart failure. Since microRNA 145 (miR-145) plays an important role in cardiac fibroblast response to wound healing and cardiac repair after an myocardial infarction (MI), using a miR-145 knock-out (KO) mouse model, we evaluated contribution of down-regulation of miR-145 to cardiac fibroblast and myofibroblast function during adverse cardiac remodelling. Cardiac function decreased more and the infarct size was larger in miR-145 KO than that in WT mice after MI and this phenomenon was accompanied by a decrease in cardiac fibroblast-to-myofibroblast differentiation. Quantification of collagen I and α-SMA protein levels as well as wound contraction revealed that transdifferentiation of cardiac fibroblasts into myofibroblasts was lower in KO than WT mice. In vitro restoration of miR-145 induced more differentiation of fibroblasts to myofibroblasts and this effect involved the target genes Klf4 and myocardin. MiR-145 contributes to infarct scar contraction in the heart and the absence of miR-145 contributes to dysfunction of cardiac fibroblast, resulting in greater infarct thinning and dilatation. Augmentation of miR-145 could be an attractive target to prevent adverse cardiac remodelling after MI by enhancing the phenotypic switch of cardiac fibroblasts to myofibroblasts.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cicatrización de Heridas
/
Diferenciación Celular
/
MicroARNs
/
Miofibroblastos
/
Infarto del Miocardio
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2020
Tipo del documento:
Article