A Glimpse of Matrix Metalloproteinases in Diabetic Nephropathy

Abstract

Matrix metalloproteinases (MMPs) are proteolytic enzymes belonging to the family of zinc-dependent endopeptidases that are capable of degrading almost all the proteinaceous components of the extracellular matrix (ECM). It is known that MMPs play a role in a number of renal diseases, such as, various forms of glomerulonephritis and tubular diseases, including some of the inherited kidney diseases. In this regard, ECM accumulation is considered to be a hallmark morphologic finding of diabetic nephropathy, which not only is related to the excessive synthesis of matrix proteins, but also to their decreased degradation by the MMPs. In recent years, increasing evidence suggest that there is a good correlation between the activity or expression of MMPs and progression of renal disease in patients with diabetic nephropathy in humans and in various experimental animal models. In such a diabetic milieu, the expression of MMPs is modulated by high glucose, advanced glycation end products (AGEs), TGF-β, reactive oxygen species (ROS), transcription factors and some of the microRNAs. In this review, we focused on the structure and functions of MMPs, and their role in the pathogenesis of diabetic nephropathy.

An extract of Pueraria tuberosa tubers attenuates diabetic nephropathy by upregulating matrix metalloproteinase‐9 expression in the kidney of diabetic rats

“…15,19 However, some reports indicate biphasic modulation of MMP-9, with initial activation followed by a decline in later stages of DN. 20 In another study, similar biphasic response is reported for activity of superoxide dismutase and catalase in pathogenesis of acute kidney injury induced by cisplatin and also hyperlipidimia induced by high fructose diet. 21 The role of MMP-9 in the secretion of growth factors and cytokines has also been reported.…”

Insights into the Mechanisms Involved in the Expression and Regulation of Extracellular Matrix Proteins in Diabetic Nephropathy

“…The relevant mechanism(s) or the molecules involved in increased ECM expression and their regulation in kidney in diabetic state has been extensively investigated. To name a few are glucose transporter proteins (GLUTs) [11], protein kinase C (PKC) [12], advanced glycation end-products (AGEs) [13], reactive oxygen species (ROS) [14], Matrix metallo-proteinases (MMPs) [15, 16], microRNA [17], growth factors/cytokines and hormones [18, 19]. The latter two would include transforming growth factor β (TGF-β), platelet-derived growth factor (PDGF), growth hormone-insulin-like growth factor (GH-IGF), connective tissue growth factor (CTGF) and Angiotensin II (Ang II) etc.…”

Matrix metalloproteinases: potential therapeutic target for diabetic neuropathic pain

“…MMPs are a family of zinc-dependent proteolytic enzymes that degrade various components of ECM and mediate ECM remodeling in vertebrates [3]. MMPs are proteolytic enzymes belonging to the family of zinc-dependent endopeptidases that are capable of degrading almost all the proteinaceous components of the ECM [4]. MMPs, collectively called matrixins, regulate also the biological activity of nonmatrix substrates such as cytokines, chemokines, receptors, growth factors and cell adhesion molecules [5].…”