NDT Advance Access originally published online on November 1, 2005
Nephrology Dialysis Transplantation 2006 21(2):299-313; doi:10.1093/ndt/gfi210
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Experimental Nephrology
Role of receptor for advanced glycation end-products and signalling events in advanced glycation end-product-induced monocyte chemoattractant protein-1 expression in differentiated mouse podocytes
1 Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan and 2 Division of Nephrology, Shanghai Second Medical University affiliated Renji Hospital, Shanghai, China
Correspondence and offprint requests to: Dr Yasuhiko Tomino. Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan. Email: yasu{at}med.juntendo.ac.jp
Background. Upregulation of local monocyte chemoattractant protein-1 (MCP-1) production is involved in glomerular damage through macrophage recruitment and activation in diabetic nephropathy. Treatment of db/db mice with soluble receptor for advanced glycation end-products (RAGE) prevented recruitment of macrophages to the glomeruli and reduced albuminuria, suggesting that binding of ligands and RAGE may be involved in MCP-1 expression. Therefore, we investigated the role of advanced glycation end-products (AGEs) in MCP-1 production by podocytes and signalling events after RAGE activation.
Methods. MCP-1 gene and protein expression were examined by using reverse transcription–polymerase chain reaction and enzyme-linked immunosorbent assay in differentiated mouse podocytes. Dichlorofluorescein-sensitive intracellular reactive oxygen species (ROS) generation was measured by confocal microscopy. RAGE, phosphorylation of mitogen-activated protein kinases, nuclear factor (NF)-
B, c-Jun and Sp1 were studied using western blotting and immunocytochemistry.
Results. Both differentiated and undifferentiated podocytes expressed RAGE. MCP-1 was induced by AGEs and carboxymethyllysine (CML) in a time-dependent and dose-dependent manner in differentiated podocytes. Neutralizing antibody for RAGE suppressed AGE- and CML-induced MCP-1 production. AGEs and CML rapidly generated intracellular ROS in podocytes. Blocking of ROS by using N-acetyl-L-cysteine abolished CML and H2O2-induced MCP-1 expression. Phosphorylated extracellular signal-regulated kinase (ERK) was found in podocytes incubated with CML and was prevented by N-acetyl-L-cysteine or 7'-amino 4 [trifluoromethyl]. PD98059, an inhibitor of ERK, partially prevented CML-induced MCP-1 gene expression. NF-B and Sp1 were translocated into the nucleus after podocytes were incubated with CML for 60 min. Parthenolide and mithramycin A, inhibitors of NF-B and Sp1, respectively, abolished CML-induced MCP-1 gene expression in a dose-dependent manner.
Conclusions. These results suggest that AGEs and CML induce MCP-1 expression in podocytes through activation of RAGE and generation of intracellular ROS. NF-B and Sp1 regulate MCP-1 gene transcription.
Keywords: AGE; ERK; MCP-1; podocyte; RAGE; ROS
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Y. Lee, C. H. Chung, C. C. Khoury, T. K. Yeo, P. E. Pyagay, A. Wang, and S. Chen The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-{beta}, increases podocyte motility and albumin permeability Am J Physiol Renal Physiol, July 1, 2009; 297(1): F85 - F94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Li, S. H. Lee, D. K. Kim, R. Jin, D.-S. Jung, S.-J. Kwak, S. H. Kim, S. H. Han, J. E. Lee, S. J. Moon, et al. Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy Am J Physiol Renal Physiol, July 1, 2009; 297(1): F200 - F209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. H. Tesch MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy Am J Physiol Renal Physiol, April 1, 2008; 294(4): F697 - F701. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Waanders, E. van den Berg, R. Nagai, I. van Veen, G. Navis, and H. van Goor Renoprotective effects of the AGE-inhibitor pyridoxamine in experimental chronic allograft nephropathy in rats Nephrol. Dial. Transplant., February 1, 2008; 23(2): 518 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Burt, G. Salvidio, E. Tarabra, F. Barutta, S. Pinach, P. Dentelli, G. Camussi, P. C. Perin, and G. Gruden The Monocyte Chemoattractant Protein-1/Cognate CC Chemokine Receptor 2 System Affects Cell Motility in Cultured Human Podocytes Am. J. Pathol., December 1, 2007; 171(6): 1789 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Soma, K. Sato, H. Saito, and Y. Tsuchiya Effect of tranilast in early-stage diabetic nephropathy Nephrol. Dial. Transplant., October 1, 2006; 21(10): 2795 - 2799. [Abstract] [Full Text] [PDF]
|
|