title: Effect of P2X7 receptor knockout on AQP-5 expression of type I alveolar epithelial cells.
abstract: P2X7 receptors, ATP-gated cation channels, are specifically expressed in alveolar epithelial cells. The pathophysiological function of this lung cell type, except a recently reported putative involvement in surfactant secretion, is unknown. In addition, P2X7 receptor-deficient mice show reduced inflammation and lung fibrosis after exposure with bleomycin. To elucidate the role of the P2X7 receptor in alveolar epithelial type I cells we characterized the pulmonary phenotype of P2X7 receptor knockout mice by using immunohistochemistry, western blot analysis and real-time RT PCR. No pathomorphological signs of fibrosis were found. Results revealed, however, a remarkable loss of aquaporin-5 protein and mRNA in young knockout animals. Additional in vitro experiments with bleomycin treated precision cut lung slices showed a greater sensitivity of the P2X7 receptor knockout mice in terms of aquaporin-5 reduction as wild type animals. Finally, P2X7 receptor function was examined by using the alveolar epithelial cell lines E10 and MLE-12 for stimulation experiments with bleomycin. The in vitro activation of P2X7 receptor was connected with an increase of aquaporin-5, whereas the inhibition of the receptor with oxidized ATP resulted in down regulation of aquaporin-5. The early loss of aquaporin-5 which can be found in different pulmonary fibrosis models does not implicate a specific pathogenetic role during fibrogenesis.
authors.affiliation: Institute of Anatomy, Medical Faculty Carl Custav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Ebeling
authors.affiliation: Institute of Anatomy, Medical Faculty Carl Custav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bläsche
authors.affiliation: Institute of Anatomy, Medical Faculty Carl Custav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Falk
authors.initials: F
authors.lastname: Hofmann
authors.affiliation: Department of Internal Medicine and Cardiology, Technische Universität Dresden, Dresden, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Augstein
authors.affiliation: Institute of Anatomy, Medical Faculty Carl Custav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kasper
authors.affiliation: Institute of Anatomy, Medical Faculty Carl Custav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Barth
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D051402:Aquaporin 5 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001761:Bleomycin / Q000494:pharmacology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D046509:Tissue Culture Techniques
chemical_list: C496038:Aqp5 protein, mouse; D051402:Aquaporin 5; D012333:RNA, Messenger; D058486:Receptors, Purinergic P2X7; D001761:Bleomycin; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate