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TRPV4 channels are essential for alveolar epithelial barrier function as protection from lung edema.
Weber, Jonas; Rajan, Suhasini; Schremmer, Christian; Chao, Yu-Kai; Krasteva-Christ, Gabriela; Kannler, Martina; Yildirim, Ali Önder; Brosien, Monika; Schredelseker, Johann; Weissmann, Norbert; Grimm, Christian; Gudermann, Thomas; Dietrich, Alexander.
Afiliación
  • Weber J; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
  • Rajan S; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
  • Schremmer C; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
  • Chao YK; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
  • Krasteva-Christ G; Institute of Anatomy and Cell Biology, School of Medicine, Saarland University, Homburg, Germany.
  • Kannler M; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
  • Yildirim AÖ; Comprehensive Pneumology Center, Institute of Lung Biology and Disease, a member of the DZL, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
  • Brosien M; Justus Liebig University Giessen, Cardio-Pulmonary Institute, University of Giessen and Marburg Lung Center, a member of the DZL, Giessen, Germany.
  • Schredelseker J; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
  • Weissmann N; Justus Liebig University Giessen, Cardio-Pulmonary Institute, University of Giessen and Marburg Lung Center, a member of the DZL, Giessen, Germany.
  • Grimm C; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
  • Gudermann T; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
  • Dietrich A; Walther Straub Institute of Pharmacology and Toxicology, a member of the German Center for Lung Research (DZL), Ludwig Maximilian University of Munich, Munich Germany.
JCI Insight ; 5(20)2020 10 15.
Article en En | MEDLINE | ID: mdl-32931478
Ischemia/reperfusion-induced edema (IRE), one of the most significant causes of mortality after lung transplantation, can be mimicked ex vivo in isolated perfused mouse lungs (IPL). Transient receptor potential vanilloid 4 (TRPV4) is a nonselective cation channel studied in endothelium; however, its role in the lung epithelium remains elusive. Here, we show enhanced IRE in TRPV4-deficient (TRPV4-/-) IPL compared with that of WT controls, indicating a protective role of TRPV4 in maintenance of the alveolar epithelial barrier. By immunohistochemistry, mRNA profiling, and electrophysiological characterization, we detected TRPV4 in bronchial epithelium, alveolar epithelial type I (ATI), and alveolar epithelial type II (ATII) cells. Genetic ablation of TRPV4 resulted in reduced expression of the water-conducting aquaporin-5 (AQP-5) channel in ATI cells. Migration of TRPV4-/- ATI cells was reduced, and cell barrier function was impaired. Analysis of isolated primary TRPV4-/- ATII cells revealed a reduced expression of surfactant protein C, and the TRPV4 activator GSK1016790A induced increases in current densities only in WT ATII cells. Moreover, TRPV4-/- lungs of adult mice developed significantly larger mean chord lengths and altered lung function compared with WT lungs. Therefore, our data illustrate essential functions of TRPV4 channels in alveolar epithelial cells and in protection from edema formation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Edema / Acuaporina 5 / Canales Catiónicos TRPV / Enfermedades Pulmonares Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: JCI Insight Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Daño por Reperfusión / Edema / Acuaporina 5 / Canales Catiónicos TRPV / Enfermedades Pulmonares Tipo de estudio: Etiology_studies Límite: Animals / Humans Idioma: En Revista: JCI Insight Año: 2020 Tipo del documento: Article Pais de publicación: Estados Unidos