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doi:10.22028/D291-42245
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Datei | Beschreibung | Größe | Format | |
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134464.2-20201012083912-covered-e0fd13ba177f913fd3156f593ead4cfd.pdf | 41,06 MB | Adobe PDF | Öffnen/Anzeigen |
Titel: | TRPV4 channels are essential for alveolar epithelial barrier function as protection from lung edema |
VerfasserIn: | 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 |
Sprache: | Englisch |
In: | |
Titel: | JCI Insight |
Bandnummer: | 5 |
Heft: | 20 |
Verlag/Plattform: | American Society for Clinical Investigation |
Erscheinungsjahr: | 2020 |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | 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. |
DOI der Erstveröffentlichung: | 10.1172/jci.insight.134464 |
URL der Erstveröffentlichung: | https://doi.org/10.1172/jci.insight.134464 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-422450 hdl:20.500.11880/37931 http://dx.doi.org/10.22028/D291-42245 |
ISSN: | 2379-3708 |
Datum des Eintrags: | 24-Jun-2024 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplemental material |
In Beziehung stehendes Objekt: | https://insight.jci.org/articles/view/134464/sd/pdf/render/1 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Anatomie und Zellbiologie |
Professur: | M - Prof. Dr. Gabriela Krasteva-Christ |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons