{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:14:05Z","timestamp":1784304845247,"version":"3.55.0"},"reference-count":58,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["GRK 2338 Project 04"],"award-info":[{"award-number":["GRK 2338 Project 04"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["TRR152 project 16"],"award-info":[{"award-number":["TRR152 project 16"]}]},{"name":"Deutsche Zentrum f\u00fcr Lungenforschung (DZL)","award":["GRK 2338 Project 04"],"award-info":[{"award-number":["GRK 2338 Project 04"]}]},{"name":"Deutsche Zentrum f\u00fcr Lungenforschung (DZL)","award":["TRR152 project 16"],"award-info":[{"award-number":["TRR152 project 16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Transient receptor potential vanilloid 4 (TRPV4) channels have been associated with numerous pulmonary pathologies, including hypertension, asthma, and acute lung injury. However, their role in the alveolar epithelium remains unclear. We performed impedance-based resistance measurements in primary differentiated alveolar epithelial type I (AT1) cells from wild-type (WT) and TRPV4-deficient (TRPV4\u2212\/\u2212) C57\/BL6J mice to detect changes in AT1 barrier integrity upon TRPV4 activation. Both pharmacological (GSK1016790A) and a low pH-driven activation of TRPV4 were quantified, and the downstream effects on adherens junctions were assessed through the Western blotting of epithelial cadherin (E-cadherin) protein levels. Importantly, a drop in pH caused a rapid decrease in AT1 barrier resistance and increased the formation of a ~35 kDa E-cadherin C-terminal fragment, with both effects significantly reduced in TRPV4\u2212\/\u2212 AT1 cells. Similarly, the pharmacological activation of TRPV4 in AT1 cells triggered an immediate transient loss of barrier resistance and the formation of the same E-cadherin fragment, which was again diminished by TRPV4 deficiency. Moreover, TRPV4-mediated E-cadherin cleavage was significantly reduced by GI254023X, an antagonist of a disintegrin and metalloprotease 10 (ADAM10). Our results confirm the role of TRPV4 in regulating alveolar epithelial barrier permeability and provide insight into a novel signaling pathway by which TRPV4-induced Ca2+ influx stimulates metalloprotease-driven ectodomain shedding.<\/jats:p>","DOI":"10.3390\/cells13201717","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T08:56:32Z","timestamp":1729155392000},"page":"1717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["TRPV4 Mediates Alveolar Epithelial Barrier Integrity and Induces ADAM10-Driven E-Cadherin Shedding"],"prefix":"10.3390","volume":"13","author":[{"given":"Lena","family":"Schaller","sequence":"first","affiliation":[{"name":"Walther Straub Institute for Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Medical Faculty, LMU-Munich, Nussbaumstrasse 26, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gudermann","sequence":"additional","affiliation":[{"name":"Walther Straub Institute for Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Medical Faculty, LMU-Munich, Nussbaumstrasse 26, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1168-8707","authenticated-orcid":false,"given":"Alexander","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Walther Straub Institute for Pharmacology and Toxicology, Member of the German Center for Lung Research (DZL), Medical Faculty, LMU-Munich, Nussbaumstrasse 26, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","first-page":"54","article-title":"The development and plasticity of alveolar type 1 cells","volume":"143","author":"Yang","year":"2016","journal-title":"Development"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2724","DOI":"10.1172\/JCI60519","article-title":"Building and maintaining the epithelium of the lung","volume":"122","author":"Rackley","year":"2012","journal-title":"J. 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