The relationship between complement C3 expression and the MUC5B genotype in pulmonary fibrosis.
Am J Physiol Lung Cell Mol Physiol
; 315(1): L1-L10, 2018 07 01.
Article
en En
| MEDLINE
| ID: mdl-29565179
ABSTRACT
The common gain-of-function MUC5B promoter variant ( rs35705950 ) is the strongest risk factor for the development of idiopathic pulmonary fibrosis (IPF). While the role of complement in IPF is controversial, both MUC5B and the complement system play a role in lung host defense. The aim of this study was to evaluate the relationship between complement component 3 (C3) and MUC5B in patients with IPF and in bleomycin-induced lung injury in mice. To do this, we evaluated C3 gene expression in whole lung tissue from 300 subjects with IPF and 175 healthy controls. Expression of C3 was higher in IPF than healthy controls {1.40-fold increase [95% confidence interval (CI) 1.31-1.50]; P < 0.0001} and even greater among IPF subjects with the highest-risk IPF MUC5B promoter genotype [TT vs. GG = 1.59-fold (95% CI 1.15-2.20); P < 0.05; TT vs. GT = 1.66-fold (95% CI 1.20-2.30); P < 0.05]. Among subjects with IPF, C3 expression was significantly higher in the lung tissue without microscopic honeycombing than in the lung tissue with microscopic honeycombing [1.40-fold increase (95% CI 1.23- 1.59); P < 0.01]. In mice, while bleomycin exposure increased Muc5b protein expression, C3-deficient mice were protected from bleomycin-induced lung injury. In aggregate, our findings indicate that the MUC5B promoter variant is associated with higher C3 expression and suggest that the complement system may contribute to the pathogenesis of IPF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Variación Genética
/
Bleomicina
/
Complemento C3
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Fibrosis Pulmonar Idiopática
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Mucina 5B
/
Genotipo
/
Pulmón
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
/
Humans
/
Middle aged
Idioma:
En
Revista:
Am J Physiol Lung Cell Mol Physiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Año:
2018
Tipo del documento:
Article