Targeting uPARAP Modifies Lymphatic Vessel Architecture and Attenuates Lymphedema.

Background: Lymphedema is an incurable disease associated with lymphatic dysfunction that causes tissue swelling and fibrosis. We investigated whether lymphedema could be attenuated by interfering with uPARAP (urokinase plasminogen activator receptor-associated protein; gene), an endocytic receptor involved in fibrosis and lymphangiogenesis.

Methods: We generated mice with lymphatic endothelial cell (LEC)-specific deficiency and compared them with constitutive knockout mice by applying a preclinical model of secondary lymphedema (SL).

AXL promotes lymphangiogenesis by amplifying VEGF-C-mediated AKT pathway.

Lymphangiogenesis has gained considerable interest due to its established role in cancer progression and dissemination of metastatic cells through lymph nodes. Deciphering the molecular mechanisms that govern lymphangiogenesis within lymph nodes holds promise for revealing novel targetable molecules and pathways to inhibit metastasis. In this study, we revealed a previously unrecognized role of AXL, a tyrosine kinase receptor, in the lymphatic vessel formation.