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Pioglitazone inhibits angiotensin II-induced atrial fibroblasts proliferation via NF-κB/TGF-β1/TRIF/TRAF6 pathway.

Abstract
The exact mechanisms underlying inhibitory effects of pioglitazone (Pio) on Angiotensin II (AngII)-induced atrial fibrosis are complex and remain largely unknown. In the present study, we examined the effect of Pio on AngII-induced mice atrial fibrosis in vivo and atrial fibroblasts proliferation in vitro. In vivo study showed that AngII infusion induced atrial fibrosis and increased expressions of Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) and tumor necrosis factor receptor associated factor 6 (TRAF6) in mice models. However, those effects could be attenuated by Pio (P<0.01). As for in vitro experiment, Pio suppressed AngII-induced atrial fibroblasts proliferation via nuclear factor-κB/transforming growth factor-β1/TRIF/TRAF6 signaling pathway in primary cultured mice atrial fibroblasts (P<0.01). In conclusion, suppression of Pio on AngII-induced atrial fibrosis might be related to its inhibitory effects on above signaling pathway.
AuthorsXiao-qing Chen, Xu Liu, Quan-xing Wang, Ming-jian Zhang, Meng Guo, Fang Liu, Wei-feng Jiang, Li Zhou
JournalExperimental cell research (Exp Cell Res) Vol. 330 Issue 1 Pg. 43-55 (Jan 01 2015) ISSN: 1090-2422 [Electronic] United States
PMID25152439 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier Inc. All rights reserved.
Chemical References
  • Adaptor Proteins, Vesicular Transport
  • NF-kappa B
  • TICAM-1 protein, mouse
  • TNF Receptor-Associated Factor 6
  • Thiazolidinediones
  • Transforming Growth Factor beta1
  • Angiotensin II
  • Pioglitazone
Topics
  • Adaptor Proteins, Vesicular Transport (metabolism)
  • Angiotensin II (pharmacology)
  • Animals
  • Cell Proliferation
  • Fibrosis (metabolism)
  • Heart Atria (pathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myofibroblasts (drug effects, metabolism, physiology)
  • NF-kappa B (metabolism)
  • Pioglitazone
  • Signal Transduction
  • TNF Receptor-Associated Factor 6 (metabolism)
  • Thiazolidinediones (pharmacology)
  • Transforming Growth Factor beta1 (metabolism)

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