GLOMERULAR ENDOTHELIAL-CELLS SYNTHESIZE COLLAGENS BUT LITTLE GELATINASE-A AND GELATINASE-B

Mesangial sclerosis is a major feature of progressive renal disease. T he mesangium contains mesangial cells and is bounded by the peripheral glomerular basement membrane and endothelial cells. Mesangial cells s ynthesize and degrade extracellular matrix. Whereas both mesangial and endothelial cells synthesize extracellular matrix components, the deg radative pathway, well studied in the former, has not been investigate d in endothelial cells. This study examines lines of all three glomeru lar cell types derived from female B6SJLF1/J mice, as well as mRNA lev els for collagens alpha 1 (I), alpha 1 (IV), alpha 3 (IV), alpha 5 (IV ), and alpha 1 (VI), laminin, tenascin, matrix metallo-proteinase-2 (M MP-2), and MMP-9. Type I and IV collagen synthesis was confirmed by en zyme-linked immunosorbent assay. MMP-2 and MMP-9 enzyme activity was m easured by zymography. It was found that glomerular endothelial cells are a significant source of collagens, laminin, and tenascin. However, they express only low levels of MMP-2 and no detectable MMP-9. Stimul ation with exogenous transforming growth factor-pr leads to a signific ant increase in collagen I, tissue inhibitors of metalloproteinase-l, and MMP-9 in conditioned media. These data suggest that glomerular end othelial cells may play an active role in extracellular matrix remodel ing in glomerular disease.