Matrix metalloproteases: Potential role in type 2 diabetic nephropathy

Abstract

Type 2 diabetes mellitus is the most common form and constitutes a majordiabetic population in all countries. The complications of diabetes mellitus(DM) include nephropathy, neuropathy, retinopathy, and cardiovascular disease. Type 2 diabetic nephropathy (DN) is a devastating complication of DM and amain cause of end-stage renal failure. Evidences show that susceptibility to Type2 DN has a significant genetic component in addition to environmental factors. In Type 2 DN, hyperglycemia-induced changes include extracellular matrix(ECM) deposition, basement membrane (BM) thickening, as well as vascularsmooth muscle and mesangial cell growth. ECM proteins are degraded byzinc-dependent endopeptidases called matrix metalloproteases (MMPs) which inturn are regulated by tissue inhibitors of metalloproteases (TIMPs). Theproteases (MMPs) and antiproteases (TIMP) offer the opportunity to identify thedeterminants of the disease that are very likely to be causative and might lead tonew therapeutics with strong molecular underpinning.