HEPARIN SELECTIVELY INHIBITS GENE-EXPRESSION OF MATRIX METALLOPROTEINASE TRANSIN IN CULTURED MESANGIAL CELLS

The aim of this study is to examine the transcriptional regulation of matrix metalloproteinase transin in glomerular mesangial cells respond ing to inflammatory cytokines and heparin. Northern blot analysis reve aled that IL-1 beta preferentially induced transin mRNA. The stimulato ry effect was not specific to transin, and upregulation of procollagen alpha 1(IV), laminin B2 and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNAs was also observed. After IL-1 stimulation, expression o f the transin transcript increased progressively for up to 48 hours, d iffering from the limited induction of procollagen alpha 1(IV) or TIMP -1. When mesangial cells were stimulated by IL-1 beta in the presence of heparin, transin expression was markedly suppressed in a dose-depen dent manner. The inhibitory effect of heparin was specific to transin, and induction of procollagen alpha 1(IV), laminin B2 or TIMP-1 by IL- 1 beta was not affected. These findings revealed the selective counter regulation by IL-1 beta and heparin of the transin expression in mesa ngial cells. (C) 1994 Academic Press, Inc.