Increased TIMP-1 activity results in increased expression of gelatinases and altered cell motility.
Matrix metalloproteinases are proteolytic enzymes which play a major role in resorption of collagen and other components of the extracellular matrix. They are controlled by specific inhibitors, so-called tissue inhibitors of metalloproteinases (TIMPs). The balance between matrix metalloproteinases and TIMPs seems to play a major role in controlling extracellular matrix homeostasis and cell migration. The influence of TIMP-1 on migration behaviour was explored in human hepatoma cells transiently and stably transfected with mouse TIMP-1, and incubated with biologically active TIMP-1. Transfection and biosynthesis were verified by Northern blotting, Western blotting, metabolic labeling, and reverse zymography. Overexpression of and incubation with TIMP-1 resulted in suppressed migration and seemed to enhance cell-cell contact. Using gelatin zymography and Western blotting we measured a significant increase of matrix metalloproteinases-2 and matrix metalloproteinases-9 in cells transfected with TIMP-1. This new phenomenon may be of important physiological significance in modulating TIMP and MMP expression. Our results indicate a functional involvement of TIMP-1 in matrix homeostasis and some automatic control in matrix turnover.
Roeb
E
E
Medizinische Klinik III, 52057 Aachen, Germany.
Winograd
R
R
Breuer
B
B
Nguyen
H
H
Matern
S
S
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002465:Cell Movement; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D012313:RNA / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D019715:Tissue Inhibitor of Metalloproteinase-1; D012313:RNA; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9