β1 integrin regulates MMP-10 dependant tubulogenesis in human lymphatic endothelial cells

Lymphatic vessel growth requires extensive remodeling of the extracellular matrix, a process hypothesized to be related to the expression and function of the matrix metalloproteinases. We used a protein based screening strategy to demonstrate increased matrix matalloproteinase-10 expression in human lymphatic endothelial cells undergoing collagen I induced tubulogenesis. Knock-down experiments showed that matrix metalloproteinase-10 regulated lymphatic endothelial cell tubulogenesis. β1 integrin signaling via the ERK/MAPK pathway increased matrix metalloproteinase-10 mRNA and protein expression in human lymphatic endothelial cells. These findings demonstrate a novel mechanism by which β1 integrin regulates matrix metalloproteinase-10 expression during lymphatic vessel remodeling.