Rat mesangial cells and matrix metalloproteinase inhibitor: inhibition of 72-kD type IV collagenase (MMP-2) and of cell proliferation.

Abstract

The synthetic inhibitor of matrix metalloproteinases (MMP) Ro 31-9790, a hydroxamic-acid derivative, was investigated for its effect on rat mesangial cells (MC) in culture. For these studies, proliferating MC with a high degree of constitutive expression of a MMP, the 72-kD Type IV collagenase (gelatinase A, MMP-2), were chosen, because they reflect aspects of an inflammatory phenotype that may occur during certain forms of glomerular inflammatory diseases. Ro 31-9790 inhibited activity of the rat MC MMP-2 in a concentration-dependent and competitive fashion, as analyzed by quantitative densitometry and by a continuously recording fluorescent assay. Furthermore, Ro 31-9790 inhibited the proliferation rate of cultured rat MC in a concentration-dependent and at least partially reversible manner without affecting cell viability. It was concluded that the application of synthetic MMP inhibitors may offer a new perspective for the therapy of mesangial cell-derived forms of glomerulonephritis.