Characterization of matrix metalloproteinases in human urine: alterations during adolescence

Matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent proteinases that have been implicated in matrix turnover under both normal and pathological conditions. Previous studies have shown that several MMPs are produced in various cell types in the kidney, suggesting that MMPs may be involved in renal morphogenesis and remodelling. Using a variety of techniques, including gelatin and casein zymography, gelatin affinity chromatography, immunoblotting, and immunoprecipitation, we have identified the major gelatinases in human urine as MMP-2 and MMP-9. Latent forms of both enzymes were detected in urine, as well as lower molecular mass species of each, consistent with activated forms of MMP-2 and MMP-9. MMP-2 and MMP-9 were also measured in individual human urine samples (n=40). No significant gender differences in MMP concentrations were detected. However, renal MMP expression appeared to be age dependent; the highest average amounts of urine MMP-2 were detected during adolescence, while the converse was true of urine MMP-9. Together, these findings indicate that under normal conditions, human urine contains MMP-2 and/or MMP-9, suggesting that these two MMPs are normally produced within the kidney, where they may regulate normal renal remodelling and matrix homeostasis in an age-specific manner.