Blockade of CCL2/CCR2 signalling ameliorates diabetic nephropathy in db/db 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

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1700-1710
Number of pages11
JournalNephrology Dialysis Transplantation
Volume28
Issue number7
DOIs
Publication statusPublished - 2013 Jul 1

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

Cite this

Seok, S. J., Lee, E. S., Kim, G. T., Hyun, M., Lee, J. H., Chen, S., Choi, R., Kim, H. M., Lee, E. Y., & Chung, C. H. (2013). Blockade of CCL2/CCR2 signalling ameliorates diabetic nephropathy in db/db mice. Nephrology Dialysis Transplantation, 28(7), 1700-1710. https://doi.org/10.1093/ndt/gfs555