title: The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma.
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/β-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/β-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 β-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking β-catenin expression with a specific siRNA attenuated airway inflammation and airway remodeling. Decreased subepithelial fibrosis and collagen accumulation in the β-catenin siRNA-treated mice was accompanied by reduced expression of transforming growth factor-β. We further showed that suppressing β-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/β-catenin signaling pathway is highly expressed and regulates the development of airway remodeling in chronic asthma.
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kwak
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Seo
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Moon
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Jang Won
authors.initials: JW
authors.lastname: Sohn
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Ho Joo
authors.initials: HJ
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
authors.forename: Sang-Heon
authors.identifier: http://orcid.org/0000-0001-8398-4444
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002908:Chronic Disease; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; C092778:WNT7A protein, human; D051153:Wnt Proteins; D051176:beta Catenin