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

Biochem Biophys Res Commun. 1998 Oct 29;251(3):681-7. doi: 10.1006/bbrc.1998.9531.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Collagen
  • Culture Media
  • Dogs
  • Enzyme Induction
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Gels
  • Hepatocyte Growth Factor / metabolism*
  • Kidney Tubules / cytology
  • Kidney Tubules / growth & development*
  • Kidney Tubules / metabolism
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / metabolism*
  • Morphogenesis / drug effects
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacology
  • Protease Inhibitors / pharmacology
  • RNA, Antisense / pharmacology
  • Thiophenes / pharmacology
  • Tissue Inhibitor of Metalloproteinase-1 / pharmacology
  • Tissue Inhibitor of Metalloproteinase-2 / pharmacology


  • Culture Media
  • Gels
  • Protease Inhibitors
  • RNA, Antisense
  • Thiophenes
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Phenylalanine
  • Hepatocyte Growth Factor
  • Collagen
  • batimastat
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases