Pioglitazone attenuates diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats

Gang Jee Ko, Young Sun Kang, Sang Youb Han, Mi Hwa Lee, Hye Kyoung Song, Kum Hyun Han, Hyoung Kyu Kim, Jee Young Han, Dae Ryong Cha

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Background. Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors that play a role in insulin sensitivity, lipid metabolism and inflammation. However, the effects of PPARγ agonist on renal inflammation have not been fully examined in type 2 diabetic nephropathy. Methods. In the present study, we investigated the effect and molecular mechanism of the PPARγ agonist, pioglitazone, on the progression of diabetic nephropathy in type 2 diabetic rats. Inflammatory markers including NF-κB, MCP-1 and pro-fibrotic cytokines were determined by RT-PCR, western blot, immunohistochemical staining and EMSA. In addition, to evaluate the direct anti-inflammatory effect of PPARγ agonist, we performed an in vitro study using mesangial cells. Results. Treatment of OLETF rats with pioglitazone improved insulin sensitivity and kidney/body weight, but had a little effect on blood pressure. Pioglitazone treatment markedly reduced urinary albumin and MCP-1 excretion, and ameliorated glomerulosclerosis. In cDNA microarray analysis using renal cortical tissues, several inflammatory and profibrotic genes were significantly down-regulated by pioglitazone including NF-κB, CCL2, TGFβ1, PAI-1 and VEGF. In renal tissues, pioglitazone treatment significantly reduced macrophage infiltration and NF-κB activation in association with a decrease in type IV collagen, PAI-1, and TGFβ1 expression. In cultured mesangial cells, pioglitazone-activated endogenous PPARγ transcriptional activity and abolished high glucose-induced collagen production. In addition, pioglitazone treatment also markedly suppressed high glucose-induced MCP-1 synthesis and NF-κB activation. Conclusions. These data suggest that pioglitazone not only improves insulin resistance, glycaemic control and lipid profile, but also ameliorates renal injury through an anti-inflammatory mechanism in type 2 diabetic rats.

Original languageEnglish
Pages (from-to)2750-2760
Number of pages11
JournalNephrology Dialysis Transplantation
Volume23
Issue number9
DOIs
Publication statusPublished - 2008 Sep

Keywords

  • Diabetic nephropathy
  • Inflammation
  • Nuclear factor-kappa B
  • PPARγ agonist
  • Type 2 diabetes

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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