Activation of gelatinase A (72-kDa type IV collagenase) induced by monensin in normal human fibroblasts

Experimental Cell Research
L LiJ L Seltzer

Abstract

In monolayer culture, fibroblasts secrete all matrix metalloproteinases, including gelatinase A (72-kDa type IV collagenase), as inactive zymogens. Whereas limited proteolysis by plasmin or other matrix metalloproteinases (MMPs) can accomplish the extracellular activation of other proenzymes in this family, gelatinase A proenzyme is uniquely refractory to cleavage by such proteinases. Previously it has been shown that fibroblasts cultured in the presumably more physiologic culture milieu of a type I collagen lattice can be induced to secrete active gelatinase A. In monolayer culture, however, the plant lectin concanavalin A will induce gelatinase A activation. Here we show that in monolayer culture activation of gelatinase A by normal fibroblasts is also induced by the sodium ionophore monensin. The monensin response is dose-dependent, time-dependent, requires protein synthesis, and is specific to gelatinase A among the secreted matrix metalloproteinases. The activator appears to be associated with cell membranes and may be membrane-type matrix metalloproteinase 1(MT-MMP1). Both mRNA and immunodetectable protein of MT-MMP1 are increased with monensin treatment while message for the protein inhibitor of gelatinase A, TIMP-2, is ...Continue Reading

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Citations

Jan 20, 2007·Poultry Science·T L FoutzG N Rowland
Jul 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·N ThéretB Clément
Mar 27, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Tomoko ShofudaAlexander W Clowes
Jan 30, 2002·Journal of Comparative Pathology·B A Mungall, C C Pollitt

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