Biochemical process of membrane-associated protein is induced by inflammatory cytokines in cultured lymphatic endothelial cells

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The present study demonstrated that inflammatory cytokines induces the ectodomain shedding of type I transmembrane proteins in cultured human lymphatic endothelial cells. ADAM17 is responsible for the shedding via the activation of MAP kinase pathway in response to vascular endothelial factor (VEGF)-A. Furthermore, the entodomain shedding of membrane-associated protein enhanced the migration of cultured lymphatic endothelial cells in response to VEGF-A. Moreover, double immunofluorescence analysis revealed that the targeted overexpression of VEGF-A promoted the ectodomain shedding of the membrane associated protein cutaneous lymphatic vessels. Therefore, these results indicate, for the first time, that lymphangiogensis is mediated by the biochemical process of membrane-binding proteins in lymphatic endothelial cells in vitro and in vivo.