The Wnt/beta-catenin signaling pathway regulates the development of airway remodeling in patients with asthma
Experimental & Molecular Medicine
;
: e198-2015.
Article
in English
| 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Asthma
/
Fibrosis
/
RNA, Messenger
/
Gene Expression Regulation
/
Chronic Disease
/
RNA, Small Interfering
/
RNA Interference
/
Wnt Proteins
/
Beta Catenin
/
Airway Remodeling
Type of study:
Prognostic study
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2015
Type:
Article
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