Nephrol Dial Transplant Vol. 19 No. 12 © ERA-EDTA 2004; all rights reserved
Original Article
Macrophages in streptozotocin-induced diabetic nephropathy: potential role in renal fibrosis
1 Department of Nephrology and 2 Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia
Correspondence and offprint requests to: Dr Greg Tesch, Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, Victoria 3168, Australia. Email: gtesch{at}hotmail.com
Background. Renal fibrosis is central to the progression of diabetic nephropathy; however, the mechanisms responsible for fibroblast and matrix accumulation in this disease are only partially understood. Macrophages accumulate in diabetic kidneys, but it is unknown whether macrophages contribute to renal fibrosis. Therefore, we examined whether macrophage accumulation is associated with the progression of renal injury and fibrosis in type 1 diabetic nephropathy and whether macrophages exposed to the diabetic milieu could promote fibroblast proliferation.
Methods. Kidney macrophages, renal injury and fibrosis were analysed in diabetic C57BL/6J mice at 2, 8, 12 and 18 weeks after streptozotocin injection. Isolated rat bone marrow macrophages were stimulated with diabetic rat serum or carboxymethyllysine (CML)-bovine serum albumin (BSA) to determine whether macrophage-conditioned medium could promote the proliferation of rat renal (NRK-49F) fibroblasts.
Results. Progressive injury and fibrosis in diabetic nephropathy was associated with increased numbers of kidney macrophages. Macrophage accumulation in diabetic mice correlated with hyperglycaemia (blood glucose, HbA1c levels), renal injury (albuminuria, plasma creatinine), histological damage and renal fibrosis (myofibroblasts, collagen IV). Culture supernatant derived from bone marrow macrophages incubated with diabetic rat serum or CML-BSA induced proliferation of fibroblasts, which was inhibited by pre-treating fibroblasts with interleukin-1 (IL-1) receptor antagonist or the platelet-derived growth factor (PDGF) receptor kinase inhibitor, STI-571.
Conclusion. Kidney macrophage accumulation is associated with the progression of renal injury and fibrosis in streptozotocin-induced mouse diabetic nephropathy. Elements of the diabetic milieu can stimulate macrophages to promote fibroblast proliferation via IL-1- and PDGF-dependent pathways which may enhance renal fibrosis.
Keywords: interleukin-1; macrophage; platelet-derived growth factor; streptozotocin-induced diabetic nephropathy; renal fibrosis
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Pang, Z. Gao, J. Yin, J. Zhang, W. Jia, and J. Ye Macrophage infiltration into adipose tissue may promote angiogenesis for adipose tissue remodeling in obesity Am J Physiol Endocrinol Metab, August 1, 2008; 295(2): E313 - E322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Menke, G. C. Zeller, E. Kikawada, T. K. Means, X. R. Huang, H. Y. Lan, B. Lu, J. Farber, A. D. Luster, and V. R. Kelley CXCL9, but not CXCL10, Promotes CXCR3-Dependent Immune-Mediated Kidney Disease J. Am. Soc. Nephrol., June 1, 2008; 19(6): 1177 - 1189. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Nacu, I. G. Luzina, K. Highsmith, V. Lockatell, K. Pochetuhen, Z. A. Cooper, M. P. Gillmeister, N. W. Todd, and S. P. Atamas Macrophages Produce TGF-{beta}-Induced ({beta}-ig-h3) following Ingestion of Apoptotic Cells and Regulate MMP14 Levels and Collagen Turnover in Fibroblasts J. Immunol., April 1, 2008; 180(7): 5036 - 5044. [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]
|
|
|
|
 |
|
 B. Lange-Sperandio, A. Trautmann, O. Eickelberg, A. Jayachandran, S. Oberle, F. Schmidutz, B. Rodenbeck, M. Homme, R. Horuk, and F. Schaefer Leukocytes Induce Epithelial to Mesenchymal Transition after Unilateral Ureteral Obstruction in Neonatal Mice Am. J. Pathol., September 1, 2007; 171(3): 861 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Sasser, J. C. Sullivan, J. L. Hobbs, T. Yamamoto, D. M. Pollock, P. K. Carmines, and J. S. Pollock Endothelin A Receptor Blockade Reduces Diabetic Renal Injury via an Anti-Inflammatory Mechanism J. Am. Soc. Nephrol., January 1, 2007; 18(1): 143 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Guo, D. Martinez-Vasquez, G. P. Mendez, M. F. Toniolo, T. M. Yao, E. M. Oestreicher, T. Kikuchi, N. Lapointe, L. Pojoga, G. H. Williams, et al. Mineralocorticoid Receptor Antagonist Reduces Renal Injury in Rodent Models of Types 1 and 2 Diabetes Mellitus Endocrinology, November 1, 2006; 147(11): 5363 - 5373. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Galkina and K. Ley Leukocyte Recruitment and Vascular Injury in Diabetic Nephropathy J. Am. Soc. Nephrol., February 1, 2006; 17(2): 368 - 377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Y. Chow, D. J. Nikolic-Paterson, E. Ozols, R. C. Atkins, and G. H. Tesch Intercellular Adhesion Molecule-1 Deficiency Is Protective against Nephropathy in Type 2 Diabetic db/db Mice J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1711 - 1722. [Abstract] [Full Text] [PDF]
|
|