The Wnt/beta-catenin signaling pathway regulates the development of airway remodeling in patients with asthma.
- Author:
Hyun Jung KWAK
1
;
Dong Won PARK
;
Ji Young SEO
;
Ji Yong MOON
;
Tae Hyung KIM
;
Jang Won SOHN
;
Dong Ho SHIN
;
Ho Joo YOON
;
Sung Soo PARK
;
Sang Heon KIM
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH: 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
- From:Experimental & Molecular Medicine 2015;47(12):e198-
- CountryRepublic of Korea
- Language:English
- 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.
