{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:35:33Z","timestamp":1792802133082,"version":"4.5.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Science and Technology Research Project of the Education Department of Jilin Province","award":["JJKH20220973KJ"],"award-info":[{"award-number":["JJKH20220973KJ"]}]},{"name":"the Joint Project of China-Japan Union Hospital and Basic Medical College of Jilin University","award":["KYXZ2022JC01"],"award-info":[{"award-number":["KYXZ2022JC01"]}],"id":[{"id":"https:\/\/ror.org\/055gkcy74","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82203696"],"award-info":[{"award-number":["82203696"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>An imbalance in lymphatic fluid, whether it is caused by generation, transport, outflow, or dysfunctional vessels, can lead to lymphedema; however, the exact pathogenesis of this disease remains unclear. To explore the mechanism, we focused on the association among TRPML1, aquaporin-3 (AQP3), and aquaporin-5 (AQP5) in human lymphatic endothelial cells (HLECs). We explored the role of TRPML1 in altering the permeability of HLECs in lymphedema. Meanwhile, we constructed a disease model using gene-knockout mice to observe the effect of TRPML1 on inflammation and fibrosis in lymphedema sites. Our results indicate that TRPML1 not only regulates the localization of AQP3, -5 to the cell membrane but also increases HLEC permeability, disrupts lymphatic fluid transport, and mediates the development of chronic inflammation at the site of lymphedema. Our study suggests that TRPML1 is a precipitating factor in lymphedema. Our findings improve the understanding of TRPML1 and aquaporins in secondary lymphedema, providing valuable insights for future research.<\/jats:p>","DOI":"10.1371\/journal.pone.0310653","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T14:01:14Z","timestamp":1733407274000},"page":"e0310653","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["TRPML1 acts as a predisposing factor in lymphedema development by regulating the subcellular localization of aquaporin-3, 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