title: Transforming growth factor-β1 induces bronchial epithelial cells to mesenchymal transition by activating the Snail pathway and promotes airway remodeling in asthma.
abstract: Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and an increase in mucous glands, which may lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we observed substantially thickened lung tissue with extensive fibrosis in ovalbumin-sensitized mice, which was interrelated with transforming growth factor-β1 (TGF-β1) expression in bronchoalveolar lavage fluid. In vitro experiments further demonstrated that TGF-β1 resulted in epithelial-mesenchymal transition (EMT) in bronchial epithelial cells, which was characterized by the expected decrease in E-cadherin expression and the increase in vimentin and α-smooth muscle actin expression, as well as the associated increase in Snail expression at mRNA and protein levels. Furthermore, the downregulation of Snail by small interfering RNA (siRNA) attenuated the TGF-β1‑induced EMT-like phenotype. Of note, a significantly increased synthesis of fibronectin was observed following TGF-β1 treatment, which further supported the hypothesis that EMT is a pivotal factor in peribronchial fibrosis. In combination, the results indicated that myofibroblasts deriving from bronchial epithelial cells via EMT may contribute to peribronchial fibrosis and that Snail may be an important factor in this phenomenon.
authors.affiliation: Department of Child Health Care, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China.
authors.forename: Zhao-Chuan
authors.initials: ZC
authors.lastname: Yang
authors.forename: Ming-Ji
authors.initials: MJ
authors.lastname: Yi
authors.forename: Ni
authors.initials: N
authors.lastname: Ran
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Fu
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Feng
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Zheng-Hai
authors.initials: ZH
authors.lastname: Qu
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001980:Bronchi / Q000473:pathology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005353:Fibronectins / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D005353:Fibronectins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1
keywords: airway  remodeling; asthma; bronchial  epithelial  cells,; Snail; transforming    growth    factor-β1; epithelial-mesenchymal    transition