Rat mesangial cells and matrix metalloproteinase inhibitor: inhibition of 72-kD type IV collagenase (MMP-2) and of cell proliferation.
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.
Steinmann-Niggli
K
K
Department of Medicine, Inselspital Bern, Switzerland.
Lukes
M
M
Marti
H P
HP
D000199:Actins / Q000037:antagonists & inhibitors; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D006877:Hydroxamic Acids; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009130:Muscle, Smooth / Q000378:metabolism; D009994:Osmolar Concentration; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C097661:Ro 31-9790; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9