The role of matrix metalloproteinases and their inhibitors in the development of renal fibrosis in the patients with diabetes mellitus

Abstract

The accumulation of components of extracellular matrix in the glomerular and interstitial compartments of the kidneys is a characteristic feature of diabetic nephropathy. The leading role in the extracellular matrix catabolism is played by matrix metalloproteinases (MMP). The activity of these enzymes is regulated by a group of inhibitors including tissue metalloproteinase inhibitors, plasminogen activator inhibitor-1, etc. Both in vivo and in vitro studies have demonstrated that a reduction of MMP activities and/or an increase of expression of MMP tissue inhibitors in the glomerular and tubular cells result in the suppression of catabolism of the components of extracellular matrix under the hyperglycemic conditions. Both circulating and urinary MMP as well as their inhibitors are considered to be new potential markers of renal fibrosis associated with diabetes mellitus. It is concluded that the directed activation of MMP and neutralization of their inhibitors provide a promising tool for the treatment of diabetic nephropathy.