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.
Kadono
Y
Y
Department of Molecular Virology and Oncology, Cancer Research Institute, Department of Urology, Department of Surgery (1), School of Medicine, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-0934, Japan.
Shibahara
K
K
Namiki
M
M
Watanabe
Y
Y
Seiki
M
M
Sato
H
H
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen; D003470:Culture Media; D004285:Dogs; D004790:Enzyme Induction; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005782:Gels; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009024:Morphogenesis / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D016372:RNA, Antisense / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology
D003470:Culture Media; D005782:Gels; D011480:Protease Inhibitors; D016372:RNA, Antisense; D013876:Thiophenes; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D010649:Phenylalanine; D017228:Hepatocyte Growth Factor; D003094:Collagen; C080985:batimastat; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases