title: Impaired self-healing capacity in airway epithelia lacking aquaporin-3.
abstract: In this study, we utilized AQP3-knockout mice as the in vivo model and AQP3-knockdown human bronchial epithelial cells (HBECs) as the in vitro model. Airway injury was experimentally induced by intra-tracheal injection of naphthalene. HE staining, transmission and scanning electron microscope were performed to evaluate self-healing capacity in vivo. Transwell and wound-healing assays were performed to evaluate epithelial cell migration in vitro. We found that both the airway epithelial cells of AQP3-knockout mice and AQP3-knockdown HBECs exhibited an obviously impaired self-healing capacity with defective epithelial cell migration through AQP3-facilitated glycerol transport. In addition, glycerol supplementation could largely correct defective injury healing and epithelial cell migration. For the first time, we found evidence for distinct defects in AQP3-deficient airway epithelial cell migration. Mechanistic analysis showed AQP3-facillitated glycerol transport plays a role in airway epithelial self-healing after injury.
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Hai-Xing
authors.initials: HX
authors.lastname: Zhu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jie-Bai
authors.initials: JB
authors.lastname: Zhou
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Zhu
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Respiratory Research Institute, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Respiratory Research Institute, Shanghai, China.
authors.forename: Yuan-Lin
authors.initials: YL
authors.lastname: Song
authors.affiliation: Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Respiratory Research Institute, Shanghai, China; State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, China. Electronic address: bai.chunxue@zs-hospital.sh.cn.
authors.forename: Chun-Xue
authors.initials: CX
authors.lastname: Bai
mesh_terms: D000818:Animals; D051400:Aquaporin 3 / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000293:injuries; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004848:Epithelium / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005990:Glycerol / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009281:Naphthalenes / Q000633:toxicity; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics*
chemical_list: C496028:Aqp3 protein, mouse; D009281:Naphthalenes; D051400:Aquaporin 3; C031721:naphthalene; D005990:Glycerol
keywords: Airway epithelial cells; Aquaporin; Glycerol; Injury; Repair