{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:35:46Z","timestamp":1789763746792,"version":"4.0.1"},"reference-count":128,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T00:00:00Z","timestamp":1727654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011680","name":"King Fahad Medical City Research Center","doi-asserted-by":"publisher","award":["023-012"],"award-info":[{"award-number":["023-012"]}],"id":[{"id":"10.13039\/501100011680","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in defective chloride ion channels. This leads to thick, dehydrated mucus that severely disrupts mucociliary clearance in the respiratory system and triggers infection that eventually is the cause of death of CF patients. Current therapeutic strategies primarily focus on restoring CFTR function, blocking epithelial sodium channels to prevent mucus dehydration, or directly targeting mucus to reduce its viscosity. Among the ion channels expressed in ciliated bronchial epithelial cells, the transient receptor potential vanilloid 4 (TRPV4) channel emerges as a significant channel in CF pathogenesis. Activation of TRPV4 channels affects the regulation of airway surface liquid by modulating sodium absorption and intracellular calcium levels, which indirectly influences CFTR activity. TRPV4 is also involved in the regulatory volume decrease (RVD) process and enhances inflammatory responses in CF patients. Here, we combine current findings on TRPV4 channel modulation as a promising therapeutic approach for CF. Although limited studies have directly explored TRPV4 in CF, emerging evidence indicates that TRPV4 activation can significantly impact key pathological processes in the disease. Further investigation into TRPV4 modulators could lead to innovative treatments that alleviate severe respiratory complications and improve outcomes for CF patients.<\/jats:p>","DOI":"10.3390\/ijms251910551","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T08:09:52Z","timestamp":1727683792000},"page":"10551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["TRPV4 Channel Modulators as Potential Drug Candidates for Cystic Fibrosis"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0584-4013","authenticated-orcid":false,"given":"Razan","family":"Orfali","sequence":"first","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"AlFaiz","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhawi","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahaf","family":"Alabdulsalam","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meaad","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara","family":"Alromaih","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Dallak","sequence":"additional","affiliation":[{"name":"King Abdulaziz Medical City, Jeddah 9515, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marah","family":"Alrahal","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh 12231, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz","family":"Alwatban","sequence":"additional","affiliation":[{"name":"College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh 13317, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Saud","sequence":"additional","affiliation":[{"name":"General Education Department, Dar Al-Hikmah University, Jeddah 22246, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Vanaki, S.M., Holmes, D., Saha, S.C., Chen, J., Brown, R.J., and Jayathilake, P.G. 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