The Wnt/beta-catenin signaling pathway regulates the development of airway remodeling in patients with asthmaopen access
- Authors
- Kwak, Hyun Jung; Park, Dong Won; Seo, Ji-Young; Moon, Ji-Yong; Kim, Tae Hyung; Sohn, Jang Won; Shin, Dong Ho; Yoon, Ho Joo; Park, Sung Soo; Kim, Sang-Heon
- Issue Date
- Dec-2015
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.47, pp.1 - 8
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 47
- Start Page
- 1
- End Page
- 8
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/155781
- DOI
- 10.1038/emm.2015.91
- ISSN
- 1226-3613
- 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.
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