Renoprotection by rosiglitazone in accelerated type 2 diabetic nephropathy: Role of STAT1 inhibition and nephrin restoration

Am J Nephrol. 2010;32(2):145-55. doi: 10.1159/000316056. Epub 2010 Jul 1.


Background: Rosiglitazone (Ros) has been shown to attenuate CXCL8 and ICAM-1 overexpression in renal tubular cells exposed to glycated albumin. The present study explores whether this can be translated into renoprotection in vivo. Uninephrectomized (Unx) type 2 diabetic db/db mice were chosen as a model of accelerated diabetic nephropathy.

Methods: Uninephrectomy was performed in 10-week-old db/db mice. They were then treated with vehicle, metformin or Ros for 8 weeks.

Results: Unx-db/db mice treated with Ros had lower serum creatinine and albuminuria, less severe glomerulosclerosis, tubulointerstitial injury, fewer infiltrating macrophages, and less proliferating nuclear antigen-positive tubular cells compared with mice treated with metformin that had a similar level of glycemic control and insulin resistance. In addition, Ros but not metformin attenuated renal cortical expression of CCL2, MIP-2, and ICAM-1 and inhibited p-STAT1 signal activation. Ros also increased glomerular nephrin expression.

Conclusions: Our results delineated the biochemical and histologic characteristics of Unx-db/db mice and demonstrated the in vivo glucose-independent anti-inflammatory mechanisms of Ros in nephropathy of accelerated murine type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cytokines / antagonists & inhibitors
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / prevention & control*
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Male
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Nephrectomy
  • Protective Agents / pharmacology*
  • Rosiglitazone
  • STAT1 Transcription Factor / antagonists & inhibitors*
  • STAT1 Transcription Factor / metabolism
  • Thiazolidinediones / pharmacology*


  • Anti-Inflammatory Agents
  • Cytokines
  • Membrane Proteins
  • Protective Agents
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Thiazolidinediones
  • nephrin
  • Rosiglitazone