Balance between matrix synthesis and degradation: a determinant of glomerulosclerosis

In glomerular health and disease, the balance between extracellular matrix (ECM) protein synthesis and degradation determines the amount of matrix that accumulates locally. While cell and whole animal regulation of ECM synthesis has been the subject of ongoing study, attention has become focused on proteases that degrade matrix components only recently. Two major ECM protease systems have been defined. The plasminogen activators (PAs) are serine proteases that have matrix-degrading capability and also activate plasminogen to plasmin. Plasmin not only degrades ECM proteins, but also may activate members of the matrix metalloproteinase (MMP) family which comprise the second major matrix-degrading system. Specific biological antagonists of both the PAs and the MMPs tightly regulate proteolysis by these enzymes. All of these enzymes and inhibitors have been detected in the kidney, and their expression may be altered to facilitate ECM accumulation in conditions associated with matrix expansion, such as glomerulosclerosis. Work is in progress to determine how these systems are regulated in the kidney and to further define their contribution to the sclerotic process.