title: Glucocorticoid dexamethasone regulates the differentiation of mouse conducting airway epithelial progenitor cells.
abstract: Inhaled glucocorticoid dexamethasone is the most effective treatment of asthma currently available. Epithelial damage and shedding represents a clear manifestation of asthmatic pathologies. However it remains unknown if dexamethasone regulates functions of airway progenitor cells that are responsible for epithelial repair. In present study Secretoglobin1a1 (Scgb1a1) lineage tracing mice were injected intraperitoneally with tamoxifen to induce the expression of green fluorescence protein (GFP) in Scgb1a1-expressing conducting airway progenitor cells. Scgb1a1-expressing progenitor cells were isolated from lungs of Scgb1a1 lineage tracing mice via flow activated cell sorting. In vitro three-dimensional matrigel culture of these progenitor cells revealed that dexamethasone has little effect on the colony forming ability of airway epithelial progenitor cells, but exhibits significant effects on the differentiation of the progenitor cells. Compared to the untreated group, dexamethasone treatment inhibited the expression of forkhead box J1 (FoxJ1) and mucin subtype A & C (Muc5Ac), but promoted the expression of calcium activated chloride channel 3 (Clca3) and cystic fibrosis transmembrane conductance regulator (Cftr). Dexamethasone-induced effects on the expression of FoxJ1, Muc5Ac and Clca3 were abolished or even reversed in the presence of RU486, an antagonist of glucocorticoid receptor, indicating that glucocorticoid receptor plays a role in the regulation of airway epithelial progenitor cells by dexamethasone. These data suggested that, though effective to reduce airway inflammation, dexamethasone treatment alone fails to fully restore the mucociliary clearance function in the treatment of asthma patients.
authors: Tianjin Haihe Hospital, Tianjin Institute of Respiratory Diseases, Tianjin 300350, China. Electronic address: huaiyong.chen@foxmail.com.
authors: Huaiyong
authors: H
authors: Chen
authors: Tianjin Haihe Hospital, Tianjin Institute of Respiratory Diseases, Tianjin 300350, China.
authors: Xin
authors: X
authors: Sun
authors: Tianjin Haihe Hospital, Tianjin Institute of Respiratory Diseases, Tianjin 300350, China.
authors: Ruo
authors: R
authors: Chi
authors: Tianjin Haihe Hospital, Tianjin Institute of Respiratory Diseases, Tianjin 300350, China.
authors: Xue
authors: X
authors: Li
authors: Department of Respiratory, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors: Jing
authors: J
authors: Feng
authors: Tianjin Haihe Hospital, Tianjin Institute of Respiratory Diseases, Tianjin 300350, China.
authors: Junping
authors: J
authors: Wu
authors: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors: Wen
authors: W
authors: Ning
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
authors: Zhixue
authors: Z
authors: Liu
authors: Tianjin Haihe Hospital, Tianjin Institute of Respiratory Diseases, Tianjin 300350, China. Electronic address: wq572004@163.com.
authors: Qi
authors: Q
authors: Wu
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014132:Trachea / Q000166:cytology* / Q000187:drug effects
chemical_list: D003907:Dexamethasone
keywords: Airway epithelium; Asthma; Dexamethasone; Differentiation; Progenitor