Increased TIMP-1 activity results in increased expression of gelatinases and altered cell motility

✍ Scribed by Elke Roeb; Ron Winograd; Bettina Breuer; Huan Nguyen; Siegfried Matern

• Book ID: 102654845
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 645 KB
• Volume: 75
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19991101)75:2<346::aid-jcb16>3.0.co;2-5

✦ Synopsis

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.