MicroRNA-27b targets gremlin 1 to modulate fibrotic responses in pulmonary cells.
J Cell Biochem
; 115(9): 1539-48, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24633904
ABSTRACT
Fibrosis is a chronic disease characterized by an excessive deposition of scar tissue in the affected organs. A central mediator of this process is transforming growth factor-ß (TGF-ß), which stimulates the production of extracellular matrix proteins such as collagens. MicroRNAs (miRNAs) have been implicated in both fibrosis as well as in TGF-ß signaling, but the extent of their regulation has not been fully defined. A functional screen was conducted using a library of miRNA inhibitors to identify miRNAs that affect TGF-ß-induced type I collagen expression, a key event in the development of fibrosis. The inhibition of one miRNA in particular, miR-27b, caused a significant increase in type I collagen expression. We found that miR-27b directly targets Gremlin 1 by binding to its 3'-UTR, reducing its mRNA levels. TGF-ß signaling decreased miR-27b expression and caused a corresponding increase in Gremlin 1 levels, suggesting that TGF-ß regulates Gremlin 1 expression in part by modulating miR-27b expression. Reducing Gremlin 1 levels by either siRNA-mediated gene silencing or by using the miR-27b mimic inhibited the expression of several genes known to be involved in fibrosis, while increasing Gremlin 1 levels by the addition of either recombinant protein or the miR-27b inhibitor enhanced the expression of these genes. In summary, we have demonstrated that miR-27b targets Gremlin 1, and that this regulation likely represents an important control point in fibrotic pathways.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos e Proteínas de Sinalização Intercelular
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MicroRNAs
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Células Epiteliais
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Fibroblastos
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Pulmão
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article