[Role of matrix metalloproteinases in the progression of renal lesions].
METALLOPROTEINASES: The progression to end-stage kidney disease is accompanied by accumulation of extracellular matrix (ECM) proteins. The degradation of ECM proteins occurs by the action of proteases, notably the matrix metalloproteinases (MMP). MMP can be classified into four major groups, such as interstitial collagenases, gelatinases, stromelysins, and membrane-type (MT)-MMP. MMP are also involved in the regulation of cell proliferation and possibly of apoptosis. In the kidney, MMP are synthesized by intrinsic glomerular cells and tubular epithelial cells.


METHODS
MMP and TIMP expression is well studied in a variety of kidney disorders, particularly in diabetes mellitus and in experimental glomerulonephritis. In diabetes mellitus, an increased plasma concentration of MMP-9 was found to represent the earliest marker of diabetic kidney disease. In anti-Thy 1.1 nephritis, a rat model of mesangial proliferative glomerulonephritis, an increase in proliferation of mesangial cells is associated with augmented expression of MMP-2 and accumulation of extracellular matrix proteins. These inflammatory features can be attenuated by a synthetic MMP inhibitor. ABNORMAL MMP AND TIMP REGULATION: The hypothesis that MMP play an important role in the progression of nephropathies is mainly based on the well known ability of MMP to degrade ECM components, on the association of altered MMP expression in a large number of kidney diseases, and on the ability of MMP-2 to induce or to sustain an inflammatory mesangial cell phenotype. However, since there are only few interventional or functional studies, uncertainty persists as to whether abnormal regulation of MMP and TIMP represents a cause or simply an effect of the respective renal diseases. A DUAL ROLE: In nephropathies, MMP appear to play a dual role as antifibrotic enzymes and as proinflammatory mediators. The exact biologic function in a given renal disorder may depend upon the level of net MMP activity and on the acuteness or the chronicity of the respective disease.
Marti
H P
HP
Département de Médecine, Inselspital Bern, Suisse.
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D048909:Diabetes Complications; D004195:Disease Models, Animal; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000201:enzymology; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases