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Updated: Aug 17, 2025

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Lymphatic endothelial cell RXRα is critical for 9-cis-retinoic acid-mediated lymphangiogenesis and prevention of
Cynthia Sung1,2, Wan Jiao3, Sun Young Park1,3
1Division of Plastic Surgery, City of Hope National Medical Center, Duarte, California, USA.
Abstract:
Secondary lymphedema is a debilitating disease characterized by abnormal soft tissue swelling and caused by lymphatic system dysfunction. 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-cis-retinoic acid (9-cisRA) 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-cisRA has been demonstrated in previous studies, the mechanism of action is not completely understood. In this study, we demonstrate that when RXRα is specifically deleted in lymphatic endothelial cells, 9-cisRA fails to induce lymphangiogenesis in vitro and prevent pathologic progression of postsurgical lymphedema in vivo. These findings demonstrate that downstream nuclear receptor RXRα plays a critical role in the therapeutic efficacy of 9-cisRA in postsurgical lymphedema.
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