[The role of matrix metalloproteinases in the pathogenesis of diabetes mellitus and progression of diabetes retinopathy]

Abstract

Matrix metalloproteinases (MMPs) comprise a family of over 20 structurally related proteins which are zinc-dependent and calcium-activated endopeptidases. The members of this family are able to degrade most extracellular matrix (ECM) proteins and are thus involved in tissue remodeling and contribute to cell migration by eliminating extracellular matrix and basement membrane barriers. Of the MMPs, MMP-2 and MMP-9 are especially active in the degradation of type IV collagen, the main constituent of the basement membrane. MMPs also cleave a variety of non-ECM proteins, including cytokines, chemokines, and growth factors. MMPs and their inhibitors (TIMPs) play important roles in physiological processes such as embryogenesis and wound healing; however, these enzymes are also involved in the pathogeneses of many diseases, such as cancer and atherosclerosis. In these pathological conditions the balance between MMPs and TIMPs shifts in favor of MMPs, resulting in excessive degradation of ECM. Research results published recently show that these enzymes can also be involved in the pathogenesis of diabetes mellitus and diabetic complications such as diabetic retinopathy. MMP-9 has the ability to degrade insulin and is able to activate IL-8, the main chemoattractant factor for neutrophils and monocytes. In addition, MMP-9 enables infl ammatory cell migration and pancreas colonization by eliminating the basement membrane barriers. Type IV collagenases are also important for endothelial cell invasion occurring during neovascularization (diabetic retinopathy), as angiogenesis needs extracellular matrix degradation; what is more, these enzymes are able to degrade pigment epithelium-derived factor, which is the principal antiangiogenic protein of the eye.