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Inflammation

, Volume 37, Issue 3, pp 729–737 | Cite as

The PPARβ/δ Agonist GW501516 Attenuates Peritonitis in Peritoneal Fibrosis via Inhibition of TAK1–NFκB Pathway in Rats

  • Xuesong Su
  • Guangyu Zhou
  • Yanqiu Wang
  • Xu Yang
  • Li Li
  • Rui Yu
  • Detian Li
Article

Abstract

Peritoneal fibrosis is a common consequence of long-term peritoneal dialysis (PD), and peritonitis is a factor in its onset. Agonist-bound peroxisome proliferator-activated receptors (PPARs) function as key regulators of energy metabolism and inflammation. Here, we examined the effects of PPARβ/δ agonist GW501516 on peritonitis in a rat peritoneal fibrosis model. Peritoneal fibrosis secondary to inflammation was induced into uremic rats by daily injection of Dianeal 4.25 % PD solutions along with six doses of lipopolysaccharide before commencement of GW501516 treatment. Normal non-uremic rats served as control, and all rats were fed with a control diet or a GW501516-containing diet. Compared to control group, exposure to PD fluids caused peritoneal fibrosis that was accompanied by increased mRNA levels of monocyte chemoattractant protein-1, tumor necrotic factor-α, and interleukin-6 in the uremic rats, and these effects were prevented by GW501516 treatment. Moreover, GW501516 was found to attenuate glucose-stimulated inflammation in cultured rat peritoneal mesothelial cells via inhibition of transforming growth factor-β-activated kinase 1 (TAK1), and nuclear factor kappa B (NFκB) signaling pathway (TAK1–NFκB pathway), a main inflammation regulatory pathway. In conclusion, inhibition of TAK1–NFκB pathway with GW501516 may represent a novel therapeutic approach to ameliorate peritonitis-induced peritoneal fibrosis for patients on PD.

KEY WORDS

GW501516 PPARβ/δ TAK1–NFκB pathway peritonitis peritoneal fibrosis 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Xuesong Su
    • 1
  • Guangyu Zhou
    • 1
  • Yanqiu Wang
    • 1
  • Xu Yang
    • 1
  • Li Li
    • 1
  • Rui Yu
    • 1
  • Detian Li
    • 1
  1. 1.Department of Nephrology, Shengjing HospitalChina Medical UniversityShenyangPeople’s Republic of China

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