MEMBRANE TYPE-1 MATRIX METALLOPROTEINASE IS INVOLVED IN THE FORMATIONOF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR-INDUCED BRANCHING TUBULES IN MADIN-DARBY CANINE KIDNEY EPITHELIAL-CELLS

Matrix metalloproteinases (MMPs) are believed to be involved in morpho genesis. Association of MMPs in a model of kidney tubulogenesis was st udied using Madin-Darby canine kidney (MDCK) epithelial cells in an in vitro morphogenetic system. MDCK cells form branching tubules in thre e-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 r educed the formation of branching tubules induced by HGF. The inductio n of membrane-type 1-matrix metalloproteinase (MT1-MMP) mRNA expressio n was observed in MDCK cells cultured in the collagen gel. Stable expr ession of MT1-MMP antisense RNA interfered with the tubule formation o f MDCK cells induced by HGF-collagen gel culture. These observations i mplicate MT1-MMP in kidney tubulogenesis and TIMP-2-specific inhibitio n suggests a direct role of MT1-MMP rather than a gelatinase A-mediate d effect. (C) 1998 Academic Press.