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

Autor: Mai Ots, Barry M. Brenner, Kang-Wook Lee, Julia L. Troy, Shinichiro Kato, Harald S. Mackenzie, Farzad Ziai, Valerie A. Luyckx
Rok vydání: 1999
Předmět:
Male
medicine.medical_specialty
Chemokine
Kidney Glomerulus
Gene Expression
Tetrazoles
Angiotensin-Converting Enzyme Inhibitors
Biology
Receptor
Angiotensin
Type 2
Receptor
Angiotensin
Type 1
enalapril
Diabetes Mellitus
Experimental
Renin-Angiotensin System
Diabetic nephropathy
Angiotensin Receptor Antagonists
candesartan
macrophage recruitment
Internal medicine
Renin–angiotensin system
medicine
Animals
Diabetic Nephropathies
RNA
Messenger
Enalapril
Rats
Wistar
Growth Substances
monocyte transmigration
Cell adhesion
Chemokine CCL2
DNA Primers
Angiotensin II receptor type 1
Base Sequence
Reverse Transcriptase Polymerase Chain Reaction
Cell adhesion molecule
Macrophages
diabetic nephropathy
Monocyte
Biphenyl Compounds
glomerular injury
medicine.disease
Rats
medicine.anatomical_structure
Endocrinology
Nephrology
biology.protein
Cytokines
Benzimidazoles
proteinuria
medicine.drug
Zdroj: Kidney International. 56(3):1037-1048
ISSN: 0085-2538
DOI: 10.1046/j.1523-1755.1999.00643.x
Popis: 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-α or interleukin-1β followed RAS inhibition, and suppression of transforming growth factor-β1 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.
Databáze: OpenAIRE
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