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

Title
The Wnt/beta-catenin signaling pathway regulates the development of airway remodeling in patients with asthma
Author
김태형
Keywords
PULMONARY ARTERIAL-HYPERTENSION; SMOOTH-MUSCLE-CELLS; WNT PATHWAY; FIBROSIS; LUNG; DISEASES; BETA; INFLAMMATION; EXPRESSION; TARGET
Issue Date
2015-12
Publisher
NATURE PUBLISHING GROUP
Citation
EXPERIMENTAL AND MOLECULAR MEDICINE, v. 47, Article number e198, Page. 1-8
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.
URI
https://www.nature.com/emm/journal/v47/n12/full/emm201591a.htmlhttp://hdl.handle.net/20.500.11754/29594
ISSN
1226-3613; 2092-6413
DOI
10.1038/emm.2015.91
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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