title: Der p 2 promotes motility of airway epithelial cell attributing to AKT/GSK3β-associated epithelial-to-mesenchymal transition.
abstract: Enhanced motility of epithelial cell plays a critical role in airway repair and remodeling involved in respiratory disorders such as asthma. Der p 2 (DP2) is a major allergen derived from Dermatophagoides pteronyssinus, the major source of indoor allergens causing airway hypersensitiveness. Herein, we hypothesized that DP2 may promote airway epithelial cell motility involved in airway remodeling. Using human bronchial cell BEAS-2B as cell model incorporating with immunoblotting and real-time quantitative PCR, our results revealed that DP2 significantly diminished epithelial marker E-cadherin and elevated mesenchymal marker vimentin and alpha-smooth muscle actin (α-SMA) in both protein and mRNA levels. Additionally, DP2 altered BEAS-2B cell morphology from cobblestone-like to fibroblast-like shape with reduced cell-cell contact. In parallel, nuclear translocation of Snail and Slug, the transcriptional repressors of E-cadherin, was increased in response to DP2. Further investigation showed that activation of AKT and extracellular response-regulated kinase 1/2 and inhibition of glycogen synthase kinase-3β (GSK3β) was involved in translocation of Snail/Slug triggered by DP2. In addition to regulation of epithelial and mesenchymal markers, DP2 enhanced cell motility of the airway epithelial cell associating with AKT/GSK3β signaling using wound healing assay and invasion assay. In conclusion, DP2 not only altered expression of E-cadherin, vimentin, and α-SMA, but also enhanced migration and invasiveness of epithelial cell, attributing to modulation of AKT/GSK3β signaling and Snail/Slug translocation. These findings also suggested that DP2 may initiate epithelial-mesenchymal transition involved in airway remodeling.
authors.affiliation: Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Lin
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Wang
authors.forename: Shao-Hsuan
authors.initials: SH
authors.lastname: Kao
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000494:pharmacology*; D060829:Arthropod Proteins / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C451163:Dermatophagoides pteronyssinus antigen p 2; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3