Membrane type 1 matrix metalloproteinase is involved in the formation of hepatocyte growth factor scatter factor induced branching tubules in Madin-Darby canine kidney epithelial cells

Matrix metalloproteinases (MMPs) are believed to be involved in morphogenesis. Association of MMPs in a model of kidney tubulogenesis was studied using Madin-Darby canine kidney (MDCK) epithelial cells in an in vitro morphogenetic system. MDCK cells form branching tubules in three-dimensional collagen gel matrix in the presence of hepatocyte growth factor (HGF). The addition of specific MMP inhibitor BB-94 and tissue inhibitor MMP (TIMP)-2 but not TIMP-1 to such collagen gel cultures reduced the formation of branching tubules induced by HGF. The induction of membrane-type 1-matrix metalloproteinase (MT1-MMP) mRNA expression was observed in MDCK cells cultured in the collagen gel. Stable expression of MT1-MMP antisense RNA interfered with the tubule formation of MDCK cells induced by HGF-collagen gel culture. These observations implicate MT1-MMP in kidney tubulogenesis and TIMP-2-specific inhibition suggests a direct role of MT1-MMP rather than a gelatinase A-mediated effect. (C) 1998 Academic Press.