The Wnt/beta-catenin signaling pathway regulates the development of airway remodeling in patients with asthma
Experimental & Molecular Medicine
;
: e198-2015.
Article
Dans Anglais
| WPRIM
| ID: wpr-228161
ABSTRACT
Airway remodeling is a key characteristic of chronic asthma, particularly in patients with a fixed airflow limitation. The mechanisms underlying airway remodeling are poorly understood, and no therapeutic option is available. The Wnt/beta-catenin signaling pathway is involved in various physiological and pathological processes, including fibrosis and smooth muscle hypertrophy. In this study, we investigated the roles of Wnt/beta-catenin signaling in airway remodeling in patients with asthma. Wnt7a mRNA expression was prominent in induced sputum from patients with asthma compared with that from healthy controls. Next, we induced a chronic asthma mouse model with airway remodeling features, including subepithelial fibrosis and airway smooth muscle hyperplasia. Higher expression of Wnt family proteins and beta-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking beta-catenin expression with a specific siRNA attenuated airway inflammation and airway remodeling. Decreased subepithelial fibrosis and collagen accumulation in the beta-catenin siRNA-treated mice was accompanied by reduced expression of transforming growth factor-beta. We further showed that suppressing beta-catenin in the chronic asthma model inhibited smooth muscle hyperplasia by downregulating the tenascin C/platelet-derived growth factor receptor pathway. Taken together, these findings demonstrate that the Wnt/beta-catenin signaling pathway is highly expressed and regulates the development of airway remodeling in chronic asthma.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Asthme
/
Fibrose
/
ARN messager
/
Régulation de l'expression des gènes
/
Maladie chronique
/
Petit ARN interférent
/
Interférence par ARN
/
Protéines de type Wingless
/
Bêta-Caténine
/
Remodelage des voies aériennes
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Femelle
/
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Experimental & Molecular Medicine
Année:
2015
Type:
Article
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