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Current Vascular Pharmacology

Editor-in-Chief

ISSN (Print): 1570-1611
ISSN (Online): 1875-6212

Targeting the MCP-1/CCR2 System in Diabetic Kidney Disease

Author(s): Sara Giunti, Federica Barutta, Paolo Cavallo Perin and Gabriella Gruden

Volume 8, Issue 6, 2010

Page: [849 - 860] Pages: 12

DOI: 10.2174/157016110793563816

Price: $65

Abstract

Diabetic nephropathy is the leading cause of end-stage renal failure in the Western World and accounts for significant morbidity and mortality in patients with diabetes. Although hyperglycaemia and hypertension are established key determinants in the development of the complication, recent studies suggest that a low-grade inflammatory response may also play a role. Monocyte Chemoattractant Protein 1 (MCP-1), a potent chemokine produced by renal cells, has emerged as a very important player in this process. Specifically, it has been shown that MCP-1 is overexpressed in the kidneys from diabetic animals. Furthermore, there is amelioration of both functional and structural abnormalities in MCP-1- knockout mice in the setting of concomitant diabetes. Over recent years the cellular mechanisms linking MCP-1 to kidney injury have been increasingly delineated and, in particular, it has become evident that MCP-1 contributes to the kidney damage not only by inducing mononuclear cell recruitment, but also by direct activation of resident renal cells. The present review focuses on the most significant advances in understanding the role of MCP-1 in diabetic kidney disease and future potential therapeutic implications.

Keywords: Monocyte chemoattractant protein 1, diabetes, kidney disease, MCP-1/CCR2 System, Diabetic Kidney Disease, Diabetic nephropathy, hyperglycaemia, hypertension, chemokine, progressive glomerulopathy, micro/macroalbuminuria, C-reactive protein, Tumor Necrosis Fac-tor, Platelet Activating Factor, Inter-leukin-6, monocyte, cardiovascular risk, glomerulosclerosis, renal damage, cysteine residues, Glomerulus, macrophage infiltration, Tubulo-Interstitium, Serum, glycosaminoglycan chains, Urine, serum glycated albumin, Urinary MCP-1, Mesangial Cells, Nuclear Factor-kB, Protein Kinase C, reactive oxygen species, angiotensin II, aldosterone, Peroxisome Proliferator-Activated Receptor, telmisartan, nifedipine, low density lipoproteins, very low density lipoproteins, Transforming Growth Factor- 1, Extracellular signal-Regulated Kinase, Connective Tissue Growth Factor, Podocytes, Phosphoinositide-3 Kinase (PI3K)-dependent mechanism, Nicotinamide Adenine Dinucleotide Phosphate, diabetic albuminuria, streptozotocin-induced diabetic mice, glomerular hypertrophy, mycophenolate mofetil, Macrophage Colony-Stimulating Fac-tor, Cytokine Induced Neutrophil Chemoattractant, Nucleosome Assembly Protein-1, Tissue Inhibitor of MetalloProte-inases, cytokines IL-1, c-Jun N-terminal Kinase, F-actin microfilaments, Tubular Cells, Cerivastatin, Immunosuppressive Therapy


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