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Increased TIMP‐1 activity results in increased expression of gelatinases and altered cell motility
Author(s) -
Roeb Elke,
Winograd Ron,
Breuer Bettina,
Nguyen Huan,
Matern Siegfried
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19991101)75:2<346::aid-jcb16>3.0.co;2-5
Subject(s) - matrix metalloproteinase , zymography , blot , extracellular matrix , gelatinase , transfection , gelatinases , microbiology and biotechnology , chemistry , cell , extracellular , motility , cell culture , biology , biochemistry , gene , genetics
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. J. Cell. Biochem. 75:346–355, 1999. © 1999 Wiley‐Liss, Inc.