The role of the mesangial cell and its matrix in the pathogenesis of diabetic nephropathy.

Mesangial cells are pericyte-like cells which are found the glomeruli of the kidney. It is well known that they have important contractile and synthetic properties regulating the function of the glomerulus. During diabetes the synthesis of various extracellular matrix (ECM) components by mesangial cells are increased. In recent years it has been recognized that degradation of ECM may also be decreased in diabetes, contributing to the process of mesangium accumulation. The major enzymes responsible for ECM degradation are a large group of enzymes collectively known as matrix metalloproteinases (MMPs). The physiology of MMPs is complex and their activity is tightly regulated at many levels. The MMPs are synthesized as proenzymes and require activation via catalytic cleavage to become fully active. In this regard it is of importance that the mesangial cell and its pericellular matrix have a very active plasminogen cascade that can liberate plasmin locally to mediate matrix degradation both directly and indirectly, by activating the MMPs. In addition, the MMPs are regulated by transforming growth factor beta (TGF-beta). There is evidence that each of these pathways regulating the matrix degradation is affected by the diabetic environment and this will be the subject of this contribution.