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Blockade of CCL2/CCR2 signalling ameliorates diabetic nephropathy in db/db mice.
MedLine Citation:
PMID:  23794669     Owner:  NLM     Status:  Publisher    
BACKGROUND: CCL2/C-C chemokine receptor 2 (CCR2) signalling is suggested to play a significant role in various kidney diseases including diabetic nephropathy. We investigated the renoprotective effect of a CCR2 antagonist, RS102895, on the development of diabetic nephropathy in a type 2 diabetic mouse model.
METHODS: Six-week-old diabetic db/db and non-diabetic db/m mice were fed either normal chow or chow mixed with 2 mg/kg/day of RS102895 for 9 weeks. We investigated the effects of CCR2 antagonism on blood glucose, blood pressure, albuminuria and the structure and ultrastructure of the kidney.
RESULTS: Diabetes-induced albuminuria was significantly improved after CCR2 antagonist treatment, and glucose intolerance was improved in the RS102895-treated diabetic mice. RS102895 did not affect blood pressure, body weight or kidney weight. Mesangial expansion, glomerular basement membrane thickening and increased desmin staining in the diabetic kidney were significantly improved after RS102895 treatment. The up-regulation of vascular endothelial growth factor mRNA expression and the down-regulation of nephrin mRNA expression were markedly improved in the kidneys of RS102895-treated diabetic mice. Increased renal CD68 and arginase II and urinary malondialdehyde in diabetes were effectively attenuated by RS102895 treatment.
CONCLUSION: Blockade of CCL2/CCR2 signalling by RS102895 ameliorates diabetic nephropathy not only by improving blood glucose levels but also by preventing CCL2/CCR2 signalling from altering renal nephrin and VEGF expressions through blocking macrophage infiltration, inflammation and oxidative stress in type 2 diabetic mice.
Su Jin Seok; Eun Soo Lee; Geun Tae Kim; Miri Hyun; Ji-Hye Lee; Sheldon Chen; Ran Choi; Hong Min Kim; Eun Young Lee; Choon Hee Chung
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-6-22
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  -     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-6-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Internal Medicine, Soon Chun Hyang University Cheonan Hospital, Cheonan, Korea.
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