Protective effects of adiponectin against renal ischemia-reperfusion injury via prostacyclin-PPARα-Heme oxygenase-1 signaling pathway

Ching Feng Cheng, Wei Shiung Lian, Sung Ho Chen, Pei Fen Lai, Hsiao Fen Li, Yi Fan Lan, Winston Teng Kuei Cheng, Heng Lin

研究成果: 雜誌貢獻文章同行評審

67 引文 斯高帕斯(Scopus)

摘要

Adiponectin (APN), a circulating adipose-derived hormone that regulates inflammation and energy metabolism, has beneficial effects on the cardiovascular disorders. Serum APN levels are lower in patients with coronary artery disease and higher in patients with chronic kidney disease. However, the precise role of APN in acute reno-vascular disease is not clear. Results of the present study show that serum APN concentration decreased after renal ischemia reperfusion (I/R) injury in mice. In addition, I/R-induced renal dysfunction (elevated serum creatinine and urea levels), inflammation (number of infiltrating neutrophils, myeloperoxidase activity), and apoptotic responses (apoptotic cell number and caspase-3 activation) were attenuated in APN-treated compared to control mice. Molecular and biochemical analysis revealed that APN up-regulates heme oxygenase-1 (HO-1) via peroxisome-proliferator-activated-receptor-α (PPARα) dependent pathway which is mediated through the enhancement of COX-2 and 6-keto PGF1α expression. Chromatin immune-precipitation assay demonstrated that APN increases the binding activity of PPARα to PPRE region of HO-1 promoter. Furthermore, APN induced HO-1 expression was only found in wild-type but not in PPARα gene deleted mice. This provides in vivo evidence that APN mediated HO-1 expression depends on PPARα regulation. In conclusion, our results provide a novel APN mediated prostacyclin-PPARα-HO-1 signaling pathway in protecting renal I/R injury.

原文英語
頁(從 - 到)239-249
頁數11
期刊Journal of Cellular Physiology
227
發行號1
DOIs
出版狀態已發佈 - 1月 2012

ASJC Scopus subject areas

  • 生理學
  • 臨床生物化學
  • 細胞生物學

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