Decrease in an anti-ageing factor, growth differentiation factor 11, in chronic obstructive pulmonary disease.
Thorax
; 72(10): 893-904, 2017 10.
Article
en En
| MEDLINE
| ID: mdl-28455454
ABSTRACT
RATIONALE Cellular senescence is observed in the lungs of patients with COPD and may contribute to the disease pathogenesis. Growth differentiation factor 11 (GDF11) belongs to the transforming growth factor ß superfamily and was recently reported to be a circulating protein that may have rejuvenating effects in mice. We aimed to investigate the amounts of GDF11 in the plasma and the lungs of patients with COPD and elucidate the possible roles of GDF11 in cellular senescence. METHODS:
The plasma levels of GDF11 were investigated in two separate cohorts by western blotting. The localisation and expression of GDF11 in the lungs were investigated by immunohistochemistry and quantitative reverse transcription PCR, respectively. The effects of GDF11 on both cigarette smoke extract (CSE)-induced cellular senescence in vitro and on elastase-induced cellular senescence in vivo were investigated.RESULTS:
The levels of plasma GDF11 in the COPD group were decreased compared with the control groups in the two independent cohorts. The levels of plasma GDF11 were significantly positively correlated with pulmonary function data. The mRNA expression of GDF11 in mesenchymal cells from the COPD group was decreased. Chronic exposure to CSE decreased the production of GDF11. Treatment with GDF11 significantly inhibited CSE-induced cellular senescence and upregulation of inflammatory mediators, partly through Smad2/3 signalling in vitro. Daily GDF11 treatment attenuated cellular senescence and airspace enlargement in an elastase-induced mouse model of emphysema.CONCLUSIONS:
The decrease in GDF11 may be involved in the cellular senescence observed in COPD.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Senescencia Celular
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Proteínas Morfogenéticas Óseas
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Enfermedad Pulmonar Obstructiva Crónica
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Factores de Diferenciación de Crecimiento
Tipo de estudio:
Prognostic_studies
Límite:
Aged
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Thorax
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón