Exp Mol Med.  2015 Dec;47(12):e198. 10.1038/emm.2015.91.

The Wnt/beta-catenin signaling pathway regulates the development of airway remodeling in patients with asthma

• Kwak HJ
• Park DW
• Seo JY
• Moon JY
• Kim TH
• Sohn JW
• Shin DH
• Yoon HJ
• Park SS
• Kim SH

• KMID: 2359885
• DOI: http://doi.org/10.1038/emm.2015.91

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.

MeSH Terms

Adult
Aged
*Airway Remodeling
Animals
Asthma/genetics/metabolism/*pathology
Chronic Disease
Female
Fibrosis
Gene Expression Regulation
Humans
Lung/metabolism/*pathology
Male
Mice, Inbred BALB C
Middle Aged
RNA Interference
RNA, Messenger/genetics
RNA, Small Interfering/genetics
Wnt Proteins/genetics
*Wnt Signaling Pathway
beta Catenin/genetics/metabolism
RNA, Messenger
RNA, Small Interfering
Wnt Proteins
beta Catenin