دورية أكاديمية
Apelin-VEGF-C mRNA delivery as therapeutic for the treatment of secondary lymphedema
| العنوان: | Apelin-VEGF-C mRNA delivery as therapeutic for the treatment of secondary lymphedema |
|---|---|
| المؤلفون: | Justine Creff, Asalaa Lamaa, Emeline Benuzzi, Elisa Balzan, Francoise Pujol, Tangra Draia-Nicolau, Manon Nougué, Lena Verdu, Florent Morfoisse, Eric Lacazette, Philippe Valet, Benoit Chaput, Fabian Gross, Regis Gayon, Pascale Bouillé, Julie Malloizel-Delaunay, Alessandra Bura-Rivière, Anne-Catherine Prats, Barbara Garmy-Susini |
| المصدر: | EMBO Molecular Medicine, Vol 16, Iss 2, Pp 386-415 (2024) |
| بيانات النشر: | Springer Nature, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | lymphedema, Apelin, VEGF-C, mRNA, Collector, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Secondary lymphedema (LD) corresponds to a severe lymphatic dysfunction leading to the accumulation of fluid and fibrotic adipose tissue in a limb. Here, we identified apelin (APLN) as a powerful molecule for regenerating lymphatic function in LD. We identified the loss of APLN expression in the lymphedematous arm compared to the normal arm in patients. The role of APLN in LD was confirmed in APLN knockout mice, in which LD is increased and associated with fibrosis and dermal backflow. This was reversed by intradermal injection of APLN-lentivectors. Mechanistically, APLN stimulates lymphatic endothelial cell gene expression and induces the binding of E2F8 transcription factor to the promoter of CCBE1 that controls VEGF-C processing. In addition, APLN induces Akt and eNOS pathways to stimulate lymphatic collector pumping. Our results show that APLN represents a novel partner for VEGF-C to restore lymphatic function in both initial and collecting vessels. As LD appears after cancer treatment, we validated the APLN-VEGF-C combination using a novel class of nonintegrative RNA delivery LentiFlash® vector that will be evaluated for phase I/IIa clinical trial. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 |
| العلاقة: | https://doaj.org/toc/1757-4684Test |
| DOI: | 10.1038/s44321-023-00017-7 |
| الوصول الحر: | https://doaj.org/article/2898d3ab95934418854620e0a800a7edTest |
| رقم الانضمام: | edsdoj.2898d3ab95934418854620e0a800a7ed |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 |
|---|---|
| DOI: | 10.1038/s44321-023-00017-7 |