title: Cyclic deformation-induced injury and differentiation of rat alveolar epithelial type II cells.
abstract: The injury and differentiation of alveolar epithelial type II cells induced by alveolar epithelial deformation play important roles in the pathophysiology of ventilator-induced lung injury and repair of the lung injury, respectively. We developed an in vitro rat model to investigate the effects of deformation amplitude, peak deformation, and minimum deformation on the viability and differentiation of type II cells. Rat primary alveolar epithelial type II cells were exposed to a variety of equibiaxial cyclic stretch protocols, and deformation-induced cell survival and differentiation were analyzed. Cell death increased when deformation consisted of change in cell surface area (ΔSA) of 0-37%, 0-50%, 12-50%, 37-50% (P=0.001, P<0.001, P<0.001, and P=0.003, respectively). When ΔSA was at 12-37% and 12-50%, mRNA transcription (P=0.034 and P=0.036) and protein expressions (P=0.008 and P=0.001) of caveolin-1 (a marker for the type I phenotype) increased, in contrast to the decrease of their mRNA transcription of surfactant protein C (a marker for the type II phenotype) (P=0.011, 0.002). These results suggest that amplitude or minimum deformation ≥ 37% ΔSA is an important cause of cell death, and amplitude ≥ 25% ΔSA promotes cell differentiation. Appropriate amplitude (25% ΔSA) can not only avoid cell death but also promote cell differentiation.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ye
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhan
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Ren
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Liu
authors.forename: Chun
authors.initials: C
authors.lastname: Yang
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology*; D000818:Animals; D015415:Biomarkers; D015153:Blotting, Western; D051242:Caveolin 1 / Q000096:biosynthesis; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002469:Cell Separation; D002470:Cell Survival / Q000502:physiology; D003627:Data Interpretation, Statistical; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D008176:Lung Volume Measurements; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010366:Peak Expiratory Flow Rate / Q000502:physiology; D011650:Pulmonary Alveoli / Q000166:cytology / Q000473:pathology* / Q000502:physiology; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015656:Respiratory Mechanics / Q000502:physiology; D013990:Tidal Volume / Q000502:physiology
chemical_list: D015415:Biomarkers; D051242:Caveolin 1; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases