Loss of miR-140 is a key risk factor for radiation-induced lung fibrosis through reprogramming fibroblasts and macrophages.
Sci Rep
; 6: 39572, 2016 12 20.
Article
em En
| MEDLINE
| ID: mdl-27996039
ABSTRACT
Radiation-induced lung fibrosis (RILF) is a common side effect for patients with thoracic cancer receiving radiation therapy. RILF is characterized by excessive collagen deposition mediated by TGF-ß1 and its downstream factor SMAD3, but the exact molecular mechanism leading to fibrosis is yet to be determined. The present study investigated the impact of miR-140 on RILF development. Herein, we first found that loss of miR-140 is a marker of fibrotic lung tissue in vivo one-year post-radiation treatment. We showed that miR-140 knockout primary lung fibroblasts have a higher percentage of myofibroblasts compared to wild type primary lung fibroblasts, and that loss of miR-140 expression leads to increased activation of TGF-ß1 signaling as well as increased myofibroblast differentiation. We also identified fibronectin as a novel miR-140 target gene in lung fibroblasts. Finally, we have shown that miR-140 deficiency promotes accumulation of M2 macrophages in irradiated lung tissues. These data suggest that miR-140 is a key protective molecule against RILF through inhibiting myofibroblast differentiation and inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões por Radiação
/
MicroRNAs
/
Reprogramação Celular
/
Fibroblastos
/
Pulmão
/
Macrófagos
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos