Correction. 9-Cis retinoic acid promotes lymphangiogenesis and enhances lymphatic vessel regeneration: therapeutic implications of 9-Cis retinoic acid for secondary lymphedema.
نویسنده
چکیده
BACKGROUND The lymphatic system plays a key role in tissue fluid homeostasis and lymphatic dysfunction caused by genetic defects, or lymphatic vessel obstruction can cause lymphedema, disfiguring tissue swelling often associated with fibrosis and recurrent infections with no available cures to date. In this study, retinoic acids (RAs) were determined to be a potent therapeutic agent that is immediately applicable to reduce secondary lymphedema. METHODS AND RESULTS We report that RAs promote proliferation, migration, and tube formation of cultured lymphatic endothelial cells by activating fibroblast growth factor receptor signaling. Moreover, RAs control the expression of cell-cycle checkpoint regulators such as p27(Kip1), p57(Kip2), and the aurora kinases through both an Akt-mediated nongenomic action and a transcription-dependent genomic action that is mediated by Prox1, a master regulator of lymphatic development. Moreover, 9-cisRA was found to activate in vivo lymphangiogenesis in animals in mouse trachea, Matrigel plug, and cornea pocket assays. Finally, we demonstrate that 9-cisRA can provide a strong therapeutic efficacy in ameliorating experimental mouse tail lymphedema by enhancing lymphatic vessel regeneration. CONCLUSION These in vitro and animal studies demonstrate that 9-cisRA potently activates lymphangiogenesis and promotes lymphatic regeneration in an experimental lymphedema model, presenting it as a promising novel therapeutic agent to treat human lymphedema patients.
منابع مشابه
Molecular Cardiology 9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema
متن کامل
9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema
Dept of Surgery; Dept of Biochemistry & Molecular Biology, Dept of Preventive Med, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine; Division of Pediatric Urology, Children’s Hospital Los Angeles & University of Southern California Keck School of Medicine, Los Angeles; Center of Eye Disease & Development, Program in Vision Science, and School of Opto...
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Background: Differentiating oligodendrocyte precursor cells (OPCs) into oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling pathways.Methods: Co...
متن کاملApoptosis of N-type neuroblastoma cells after differentiation with 9-cis-retinoic acid and subsequent washout.
BACKGROUND The overall survival rate for patients with neuroblastoma has improved over the past two decades, but long-term survival for the subgroup of patients with high-risk disease remains low. In recent years, there has been interest in the potential clinical use of drugs able to induce differentiation of neuroblastoma cells. Since 9-cis-retinoic acid induces better and more sustained diffe...
متن کاملThe resolution of lymphedema by interstitial flow in the mouse tail skin.
Lymphangiogenesis is considered a promising approach for increasing fluid drainage during secondary lymphedema. However, organization of lymphatics into functional capillaries may be dependent upon interstitial flow (IF). The present study was undertaken to determine the importance of lymphangiogenesis for lymphedema resolution. We created a lymphatic obstruction that produces lymphedema in mou...
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ورودعنوان ژورنال:
- Circulation
دوره 125 7 شماره
صفحات -
تاریخ انتشار 2012