The expression and function of Gpnmb in lymphatic endothelial cells.

The lymphatic system functions in fluid homeostasis, lipid absorption and the modulation of the immune response. The role of Gpnmb (osteoactivin), an established osteoinductive molecule with newly identified anti-inflammatory properties, has not been studied in lymphangiogenesis. Here, we demonstrate that Gpnmb increases lymphatic endothelial cell (LEC) migration and lymphangiogenesis marker gene expression in vitro by enhancing pro-autophagic gene expression, while no changes were observed in cell proliferation or viability. In addition, cellular spreading and cytoskeletal reorganization was not altered following Gpnmb treatment. We show that systemic Gpnmb overexpression in vivo leads to increases in lymphatic tubule number per area. Overall, data presented in this study suggest Gpnmb is a positive modulator of lymphangiogenesis.