Association between endothelin-1/endothelin receptor A and inflammation in mouse kidneys following acute ischemia/reperfusion
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- Published online on: December 30, 2014 https://doi.org/10.3892/mmr.2014.3138
- Pages: 3981-3987
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Abstract
Renal ischemia/reperfusion (I/R) is a common risk factor for renal failure. Expression of endothelin‑1 (ET‑1) and its receptor ETA were also reported to be involved in the development of acute and chronic renal disease. The present study was designed to investigate the association between inflammation and ET‑1/ETA expression in mouse kidneys following acute I/R. The results demonstrated that acute renal I/R caused a significant increase in ET‑1 and ETA gene and transcriptional levels compared with those of the sham group (P<0.01). Ischemia alone also resulted in a marked increase of ET‑1 and ETA expression compared with that of the sham group (P<0.05). In addition, ET‑1 and ETA expression was significantly increased in the I/R group compared with that of the ischemia group (P<0.05 or P<0.01). Of note, the altered expression levels of inflammatory cytokines tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 in kidneys following I/R and ischemia alone were correlated with the expression of ET‑1 and ETA. Hypoxia is the most important stimulus of I/R for tissue injury. In kidneys, ET‑1 is primarily produced by renal glomerular endothelial cells (RGECs). In the present study, treatment with hypoxia alone or hypoxia/reoxygenation were found to increase ET‑1 and ETA expression in human RGECs (P<0.05 or P<0.01). In order to elucidate the role of inflammation in the ischemia‑ and hypoxia‑induced upregulation of ET‑1 and ETA, human RGECs were exposed to different concentrations of TNF‑α. As expected, TNF‑α increased ET‑1 and ETA expression in a dose‑dependent manner; furthermore, application of the TNF‑α inhibitor CAY10500 partially inhibited hypoxia‑induced ET‑1 and ETA expression. In conclusion, these results indicated that I/R induced upregulation of ET‑1 and ETA in the kidneys, which was, at least in part, dependent on the production of inflammatory cytokines.
