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 th e kidney. It is well known that they have important contractile and synthet ic properties regulating the function of the glomerulus. During diabetes th e synthesis of various extracellular matrix (ECM) components by mesangial c ells are increased. In recent years it has been recognized that degradation of ECM may also be decreased in diabetes, contributing to the process of m esangium accumulation. The major enzymes responsible for ECM degradation ar e a large group of enzymes collectively known as matrix metalloproteinases (MMPs). The physiology of MMPs is complex and their activity is tightly reg ulated at many levels. The MMPs are synthesized as proenzymes and require a ctivation 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 media te matrix degradation both directly and indirectly, by activating the MMPs. In addition, the MMPs are regulated by transforming growth factor beta (TG F-beta). There is evidence that each of these pathways regulating the matri x degradation is affected by the diabetic environment and this will be the subject of this contribution.