miR-218 regulates focal adhesion kinase-dependent TGFß signaling in fibroblasts.
Mol Biol Cell
; 25(7): 1151-8, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24501422
ABSTRACT
Scarring, which occurs in essentially all adult tissue, is characterized by the excessive production and remodeling of extracellular matrix by α-smooth muscle actin (SMA)-expressing myofibroblasts located within connective tissue. Excessive scarring can cause organ failure and death. Oral gingivae do not scar. Compared to dermal fibroblasts, gingival fibroblasts are less responsive to transforming growth factor ß (TGFß) due to the reduced expression, due to the reduced expression and activity of focal adhesion kinase (FAK) by this cell type. Here we show that, compared with dermal fibroblasts, gingival fibroblasts show reduced expression of miR-218. Introduction of pre-miR-218 into gingival fibroblasts elevates FAK expression and, via a FAK/src-dependent mechanism, results in the ability of TGFß to induce α-SMA. The deubiquitinase cezanne is a direct target of miR-218 and has increased expression in gingival fibroblasts compared with dermal fibroblasts. Knockdown of cezanne in gingival fibroblasts increases FAK expression and causes TGFß to induce α-smooth muscle actin (α-SMA). These results suggest that miR-218 regulates the ability of TGFß to induce myofibroblast differentiation in fibroblasts via cezanne/FAK.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fator de Crescimento Transformador beta
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MicroRNAs
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Proteína-Tirosina Quinases de Adesão Focal
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Fibroblastos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article