Elevation of Serum Levels of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-1 and Type IV Collagen, and Plasma Levels of Metalloproteinase-9 in Polycystic Kidney Disease

Abstract

Several studies on polycystic kidney disease (PKD) have revealed a number of extracellular matrix (ECM) abnormalities, suggesting that an abnormal ECM plays a role in the development of tubular cysts. Cystic kidney tubules synthesize and secrete high levels of metalloproteinases (MMP), which may participate in the restructuring of the tubular basement membrane. The aim of the present study was to determine whether serum MMP-1, tissue inhibitor of metalloproteinase (TIMP)-1, and type IV collagen levels, and plasma MMP-9 levels were altered in patients with PKD. Sixteen patients with autosomal dominant polycystic kidney disease, and 20 healthy controls were included in this study. Specific enzyme immunoassays were used to measure MMP-1, MMP-9, TIMP-1, and type IV collagen levels. Serum MMP-1 (14.8 ± 3.6 ng/ml), TIMP-1 (288.6 ± 48.6 ng/ml), and type IV collagen (192.6 ± 38.8 ng/ml) concentrations, and plasma MMP-9 (90.2 ± 26.8 ng/ml) concentrations in patients with PKD were significantly higher than those in healthy controls (MMP-1; 6.6 ± 0.9 ng/ml, p < 0.01, MMP-9; 36.4 ± 12.2 ng/ml, p < 0.01, TIMP-1; 164.6 ± 22.8 ng/ml, p < 0.01, and type IV collagen; 86.6 ± 14.2 ng/ml, p < 0.001). The present results suggest that ECM abnormalities associated with cystic kidney may result from aberrant degradation as well as from abnormal synthesis of ECM components.