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Despite a high prevalence of secondary lymphedema after cancer treatments, current management is supportive and there are no approved therapeutic agents that can thwart disease progression. We have previously demonstrated that 9\u2010cis\u2010retinoic acid (9\u2010\n                    <jats:italic>cis<\/jats:italic>\n                    RA) has the potential to be repurposed for lymphedema as it mitigates disease by promoting lymphangiogenesis at the site of lymphatic injury. Although the efficacy of 9\u2010\n                    <jats:italic>cis<\/jats:italic>\n                    RA has been demonstrated in previous studies, the mechanism of action is not completely understood. In this study, we demonstrate that when RXR\u03b1 is specifically deleted in lymphatic endothelial cells, 9\u2010\n                    <jats:italic>cis<\/jats:italic>\n                    RA fails to induce lymphangiogenesis in vitro and prevent pathologic progression of postsurgical lymphedema in vivo. These findings demonstrate that downstream nuclear receptor RXR\u03b1 plays a critical role in the therapeutic efficacy of 9\u2010\n                    <jats:italic>cis<\/jats:italic>\n                    RA in postsurgical lymphedema.\n                  <\/jats:p>","DOI":"10.1096\/fj.202200146rr","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T10:00:56Z","timestamp":1671098456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Lymphatic endothelial cell\n                    <scp>RXR\u03b1<\/scp>\n                    is critical for 9\u2010cis\u2010retinoic acid\u2010mediated lymphangiogenesis and prevention of secondary lymphedema"],"prefix":"10.1096","volume":"37","author":[{"given":"Cynthia","family":"Sung","sequence":"first","affiliation":[{"name":"Division of Plastic Surgery City of Hope National Medical Center  Duarte California USA"},{"name":"Keck School of Medicine 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