Adipogenic differentiation of human mesenchymal stromal cells is down-regulated by microRNA-369-5p and up-regulated by microRNA-371.
J Cell Physiol
; 226(9): 2226-34, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21660946
ABSTRACT
Long-term culture of human mesenchymal stromal cells (MSC) has implications on their proliferation and differentiation potential and we have demonstrated that this is associated with up-regulation of the five microRNAs miR-29c, miR-369-5p, miR-371, miR-499, and let-7f. In this study, we examined the role of these senescence-associated microRNAs for cellular aging and differentiation of MSC. Proliferation was reduced upon transfection with miR-369-5p, miR-371, and miR-499. Adipogenic differentiation was impaired by miR-369-5p whereas it was highly increased by miR-371. This was accompanied by respective gene expression changes of some adipogenic key molecules (adiponectin and fatty acid-binding protein 4 [FABP4]). Furthermore luciferase reporter assay indicated that FABP4 is a direct target of miR-369-5p. Microarray analysis upon adipogenic or osteogenic differentiation revealed down-regulation of several microRNAs albeit miR-369-5p and miR-371 were not affected. Expression of the de novo DNA methyltransferases DNMT3A and DNMT3B was up-regulated by transfection of miR-371 whereas expression of DNMT3A was down-regulated by miR-369-5p. In summary, we identified miR-369-5p and miR-371 as antagonistic up-stream regulators of adipogenic differentiation and this might be indirectly mediated by epigenetic modifications.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regulação para Baixo
/
Regulação para Cima
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MicroRNAs
/
Adipogenia
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Células-Tronco Mesenquimais
Limite:
Humans
Idioma:
En
Revista:
J Cell Physiol
Ano de publicação:
2011
Tipo de documento:
Article