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 tec hniques, including gelatin and casein zymography, gelatin affinity chromato graphy, immunoblotting, and immunoprecipitation, we have identified the maj or gelatinases in human urine as MMP-2 and MMP-9. Latent forms of both enzy mes 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 gend er differences in MMP concentrations were detected. However, renal MMP expr ession appeared to be age dependent; the highest average amounts of urine M MP-2 were detected during adolescence, while the converse was true of urine MMP-9. Together, these findings indicate that under normal conditions, hum an urine contains MMP-2 and/or MMP-9, suggesting that these two MMPs are no rmally produced within the kidney, where they may regulate normal renal rem odelling and matrix homeostasis in an age-specific manner.