Human matrix metalloproteinases: characteristics and pathologic role in altering mesangial homeostasis

Matrix metalloproteinases are zinc dependent endopeptidases belonging to the M10 family of the metalloproteinase superfamily. They are ubiquitous enzymes, structurally and functionally related, with a high degree of sequence homology. They are primarily involved in extracellular matrix (ECM) turn-over and cell migration through their expanding repertoire of substrate affinities. Twenty three different forms of human MMPs have been described to be arranged in eight distinct structural classes. Their interactions with tissue inhibitors of metalloproteinases (TIMPs), and other indigenous inhibitors have been well documented. This manuscript reviews pertinent information available on matrix metalloproteinases and TIMPs in the literature. Light chain-mediated glomerular injury represents an excellent example of how metalloproteinases participate in altering mesangial homeostasis. Investigations regarding these conditions have shown that the physico-chemical characteristics of the light chains govern the pattern of renal damage that will ensue with the mesangium representing the critical site where pathological alterations are centered. The mesangium is either replaced or expanded depending on the light chains involved in the pathologic process.