{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T10:40:05Z","timestamp":1745232005192,"version":"3.40.4"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Actio Biosciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pathogenic mutations in the Transient Receptor Potential Vanilloid 4 (TRPV4) gene cause two classes of rare autosomal dominant disorders: peripheral neuropathies and skeletal dysplasias. Although most TRPV4 pathogenic mutations increase ion flux, it remains unclear how different mutations in TRPV4 cause such distinct disease presentations. Through an in vitro cell impedance platform, we showed that TRPV4 overactivity leads to cell barrier disruption, while pharmacological or genetic inhibition of TRPV4 activity protects against barrier disruption. Unexpectedly, we find that mutations causing peripheral neuropathies and metatropic dysplasias are more likely to cause barrier disruption than mutations causing non-metatropic skeletal dysplasia presentations. Finally, we show that a novel TRPV4 inhibitor (ABS-0872) protects cell-barrier disruption and promotes recovery of barrier integrity after damage caused by TRPV4 mutations.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf023","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T12:46:46Z","timestamp":1739882806000},"page":"806-820","source":"Crossref","is-referenced-by-count":0,"title":["The impact of TRPV4 pathogenic mutations on barrier integrity"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9955-258X","authenticated-orcid":false,"given":"Gabriela","family":"Sampaio","sequence":"first","affiliation":[{"name":"Actio Biosciences, 11202 El Camino Real, Suite 100, San Diego, California, 92130 ,","place":["United States of America"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor","family":"Ismaili","sequence":"additional","affiliation":[{"name":"Actio Biosciences, 11202 El Camino Real, Suite 100, San Diego, California, 92130 ,","place":["United States of America"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Torkamani","sequence":"additional","affiliation":[{"name":"Actio Biosciences, 11202 El Camino Real, Suite 100, San Diego, California, 92130 ,","place":["United States of America"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David G","family":"Breckenridge","sequence":"additional","affiliation":[{"name":"Actio Biosciences, 11202 El Camino Real, Suite 100, San Diego, California, 92130 ,","place":["United States of America"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Katana","sequence":"additional","affiliation":[{"name":"Actio Biosciences, 11202 El Camino Real, Suite 100, San Diego, California, 92130 ,","place":["United States of America"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David B","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Actio 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