CHANGES IN MATRIX METALLOPROTEINASES DURING THE EVOLUTION OF INTERSTITIAL RENAL FIBROSIS IN A RAT EXPERIMENTAL-MODEL

The aim of the present study was to analyze the matrix metalloproteina se (MMP) activity during the evolution of interstitial renal fibrosis in a rat experimental model of unilateral ureteral obstruction. The in terstitial type I collagenase and the gelatinolytic activities were an alyzed by radiolabeled substrate degradation. Interstitial collagenase activity was low at all times while gelatinolytic activity increased on day 6 of evolution, with a decrease in activity from this point. Th e use of organomercurials revealed the presence of latent enzyme in al l cases. Normal kidney samples contained MMP-9 in both active and proe nzyme forms as revealed by zymography. On day 3 MMP-9 dimers appeared, and increased activity was observed until day 6. A decrease in the ge latinolytic activity was detected from days 9-15 of evolution. This ob servation was confirmed by Western blot analysis that revealed the pre sence of proMMP-9 mainly from days 6-12. Tissue inhibitor of metallopr oteinase-l (TIMP-1) was also detected alone and in combination with pr oMMP-1 and MMP-1, particularly from days 6-15 of evolution. The presen ce of MMP-9 and MMP-1 was detected in the cytoplasm of cortical tubula r cells by immunohistochemistry, with no difference between the experi mental and the normal kidneys. There was also an increase in collagen concentration from day 3 after surgery that increased during the entir e evolution of the experimental model. This work reveals that the decr ease in the MMP-9 and MMP-1 enzymatic activity, due to their interacti on with TIMP-1 and to the lack of activation of the latent forms, may participate in the excessive collagen deposit during the evolution of experimental interstitial renal fibrosis.