Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats.

BACKGROUND Glomerular macrophage accumulation in diabetes implicates monocyte recruitment mechanisms in the pathogenesis of diabetic nephropathy. To test the hypothesis that overexpression of monocyte chemoattractant protein-1 (MCP-1), a monocyte chemoattractant, is attenuated by renin-angiotensin system (RAS) inhibition, we assessed expression of genes regulating monocyte transmigration in the glomeruli of diabetic rats. METHODS Competitive reverse transcription-polymerase chain reaction (RT-PCR) was used to semiquantitate mRNA expression in glomeruli harvested by sieving at serial intervals after the induction of diabetes by streptozotocin in Munich-Wistar rats. Although subject to limitations, competitive RT-PCR provides an objective measure suited to the minute quantities of RNA extractable from glomerular isolates. RESULTS Time-dependent elevation of MCP-1 expression was dramatically suppressed by treatment with the angiotensin-converting enzyme inhibitor enalapril or the AT1 receptor antagonist candesartan, and was closely associated with effects on proteinuria and glomerular macrophage number. By contrast, no sustained suppression of the cell adhesion molecules intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 or the classic MCP-1 stimulators tumor necrosis factor-alpha or interleukin-1beta followed RAS inhibition, and suppression of transforming growth factor-beta1 expression was transient. CONCLUSION These data suggest that glomerular macrophage recruitment in experimental diabetes is largely determined by angiotensin-stimulated MCP-1 expression. We conclude that the RAS is an important regulator of local MCP-1 expression, either directly or through glomerular hemodynamic effects, and that our data strongly implicate macrophage recruitment and activation in the pathogenesis of early diabetic glomerular injury.

[1]  W. R. Taylor,et al.  Monocyte chemoattractant protein-1 expression in aortic tissues of hypertensive rats. , 1997, Hypertension.

[2]  W. Border,et al.  Angiotensin II in renal fibrosis: should TGF-beta rather than blood pressure be the therapeutic target? , 1997, Seminars in nephrology.

[3]  M. Cooper,et al.  Transforming growth factor β1 and renal injury following subtotal nephrectomy in the rat: Role of the renin-angiotensin system , 1997 .

[4]  H. Abboud,et al.  Expression of Transforming Growth Factor-β and Type IV Collagen in Early Streptozotocin-Induced Diabetes , 1997, Diabetes.

[5]  J. Moran,et al.  Focal glomerulosclerosis in the remnant kidney model--an inflammatory disease mediated by cytokines. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[6]  B. Brenner,et al.  Nephron mass modulates the hemodynamic, cellular, and molecular response of the rat renal allograft. , 1997, Transplantation.

[7]  M. Fujishima,et al.  Transforming growth factor-beta 1 in hypertensive renal injury in Dahl salt-sensitive rats. , 1996, Journal of the American Society of Nephrology : JASN.

[8]  G. Beck,et al.  Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. Diabetic Renal Disease Study Group. , 1996, The New England journal of medicine.

[9]  Y. Akai,et al.  Quantification of glomerular TGF-β1 mRNA in patients with diabetes mellitus , 1996 .

[10]  H. Yokoyama,et al.  Central Role of TGF‐β in the Pathogenesis of Diabetic Nephropathy and Macrovascular Complications: A Hypothesis , 1996 .

[11]  J. Lebreton,et al.  Differential expression of cytokine genes in monocytes, peritoneal macrophages and liver following endotoxin- or turpentine-induced inflammation in rat. , 1996, Cytokine.

[12]  H. Schmid,et al.  Transforming growth factor-beta in the development of rat diabetic nephropathy. A 10-month study with insulin-treated rats. , 1996, Nephron.

[13]  K. Nadeau,et al.  Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  K. Sharma,et al.  Role of transforming growth factor-beta in diabetic glomerulosclerosis and renal hypertrophy. , 1995, Kidney international. Supplement.

[15]  T. Meyer,et al.  Endothelial cell injury initiates glomerular sclerosis in the rat remnant kidney. , 1995, The Journal of clinical investigation.

[16]  S. Klahr,et al.  Role of angiotensin II in the tubulointerstitial fibrosis of obstructive nephropathy. , 1995, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[17]  M. Ketteler,et al.  TGF-beta: a cytokine mediator of glomerulosclerosis and a target for therapeutic intervention. , 1995, Kidney international. Supplement.

[18]  F N Ziyadeh,et al.  Prevention of diabetic nephropathy in db/db mice with glycated albumin antagonists. A novel treatment strategy. , 1995, The Journal of clinical investigation.

[19]  C. Alpers,et al.  Cellular events in the evolution of experimental diabetic nephropathy. , 1995, Kidney international.

[20]  R. Klein,et al.  Markers of Cardiac Hypertrophy a , 1995, Annals of the New York Academy of Sciences.

[21]  J. Mannhalter,et al.  Video image analysis of quantitative competitive PCR products: comparison of different evaluation methods. , 1995, BioTechniques.

[22]  M. Ketteler,et al.  Transforming growth factor-beta and angiotensin II: the missing link from glomerular hyperfiltration to glomerulosclerosis? , 1995, Annual review of physiology.

[23]  B. Rovin,et al.  Glomerular expression of monocyte chemoattractant protein-1 in experimental and human glomerulonephritis. , 1994, Laboratory investigation; a journal of technical methods and pathology.

[24]  G. Striker,et al.  Advanced glycation end products up-regulate gene expression found in diabetic glomerular disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  K. Thai,et al.  Expression of transforming growth factor-β1 during diabetic renal hypertrophy , 1994 .

[26]  S. Kagami,et al.  Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. , 1994, The Journal of clinical investigation.

[27]  S Chien,et al.  Fluid shear stress induces a biphasic response of human monocyte chemotactic protein 1 gene expression in vascular endothelium. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[28]  K. Sharma,et al.  Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-beta. , 1994, The Journal of clinical investigation.

[29]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. , 1993 .

[30]  R. Bain,et al.  The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. , 1993, The New England journal of medicine.

[31]  F. Thaiss,et al.  Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis. , 1993, Kidney international.

[32]  J. Lenormand,et al.  Isolation and characterization of a cDNA clone encoding for rat CSF-1 gene. Post-transcriptional repression occurs in myogenic differentiation. , 1993, Biochimica et biophysica acta.

[33]  N. Perico,et al.  Short- and long-term effect of angiotensin II receptor blockade in rats with experimental diabetes. , 1993, Journal of the American Society of Nephrology : JASN.

[34]  K. Yoshinaga,et al.  The role of macrophages in diabetic glomerulosclerosis. , 1993, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[35]  E Ruoslahti,et al.  Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[36]  G. Gibbons,et al.  Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II. , 1992, The Journal of clinical investigation.

[37]  M. Cybulsky,et al.  Nucleotide sequence of rat vascular cell adhesion molecule-1 cDNA. , 1992, Biochimica et biophysica acta.

[38]  Y. Kita,et al.  Sequence and expression of rat ICAM-1. , 1992, Biochimica et biophysica acta.

[39]  B. Rovin,et al.  Cytokine-induced production of monocyte chemoattractant protein-1 by cultured human mesangial cells. , 1992, Journal of immunology.

[40]  M. Rocco,et al.  Elevated glucose stimulates TGF-beta gene expression and bioactivity in proximal tubule. , 1992, Kidney international.

[41]  E. Friedman,et al.  Advanced glycosylation end products in patients with diabetic nephropathy. , 1991, The New England journal of medicine.

[42]  Jennifer K. Adams,et al.  A relationship between proteinuria and acute tubulointerstitial disease in rats with experimental nephrotic syndrome. , 1991, The American journal of pathology.

[43]  T. Yoshimura,et al.  Molecular cloning of rat monocyte chemoattractant protein-1 (MCP-1) and its expression in rat spleen cells and tumor cell lines. , 1991, Biochemical and biophysical research communications.

[44]  Tabbara Ia,et al.  Hematopoietic growth factors. , 1991 .

[45]  A. Sica,et al.  Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor. , 1990, Journal of immunology.

[46]  C. Alpers,et al.  Platelets mediate glomerular cell proliferation in immune complex nephritis induced by anti-mesangial cell antibodies in the rat. , 1990, The American journal of pathology.

[47]  B. Brenner,et al.  Short and long term effects of antihypertensive therapy in the diabetic rat. , 1989, Kidney international.

[48]  B. Chavers,et al.  Mesangial Expansion as a Central Mechanism for Loss of Kidney Function in Diabetic Patients , 1989, Diabetes.

[49]  E. Appella,et al.  Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. , 1989, Journal of immunology.

[50]  D. Kaiser,et al.  T-cells and macrophages in rapidly progressive glomerulonephritis: clinicopathologic correlations. , 1987, Kidney international.

[51]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[52]  B. Brenner,et al.  Prevention of diabetic glomerulopathy by pharmacological amelioration of glomerular capillary hypertension. , 1986, The Journal of clinical investigation.

[53]  B. Brenner,et al.  Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[54]  K. Seyer-Hansen Renal hypertrophy in experimental diabetes mellitus. , 1983, Kidney international.

[55]  R. Atkins,et al.  A comparison of fixatives and immunohistochemical technics for use with monoclonal antibodies to cell surface antigens. , 1982, American journal of clinical pathology.

[56]  J. Christiansen,et al.  Kidney function and size in diabetics before and during initial insulin treatment. , 1982, Kidney international.

[57]  B. Brenner,et al.  Glomerular hemodynamics in experimental diabetes mellitus. , 1981, Kidney international.

[58]  Mogensen Ce Glomerular Filtration Rate and Renal Plasma Flow in Short-term and Long-term Juvenile Diabetes Mellitus , 1971 .