Angiotensin II mediates urotensin II expression by hypoxia in cultured cardiac fibroblast

Kou Gi Shyu, Bao Wei Wang, Wei Jan Chen, Peiliang Kuan, Chiu Mei Lin*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations


Background Urotensin II plays a role in myocardial remodelling. Cardiac fibroblasts play a critical role in the development of cardiac fibrosis. The effect of hypoxia on urotensin II expression in cardiac fibroblasts is poorly understood. We sought to investigate the regulation of urotensin II by hypoxia in cardiac fibroblasts and the effect of angiotensin II in the interaction with urotensin II. Methods and results Rat cardiac fibroblasts were cultured in hypoxic chamber. Hypoxia significantly increased urotensin II expression and reactive oxygen species (ROS) production in cultured cardiac fibroblasts. Hypoxia-induced increase in urotensin II protein and ROS was significantly attenuated after the addition of SP600125, JNK siRNA or N-acetylcysteine before hypoxia treatment. The phosphorylated JNK protein was induced by hypoxia and was abolished by pretreatment with SP600125, losartan (an angiotensin II receptor antagonist) or N-acetylcysteine. The increased urotensin II expression by exogenous addition of angiotensin II was similar to that by hypoxia. Addition of losartan and angiotensin II antibody before hypoxia almost completely inhibited the increase in urotensin II induced by hypoxia. Hypoxia significantly increased the secretion of angiotensin II from cardiac fibroblasts and increased the collagen I protein expression. Hypoxia significantly increased the urotensin II promoter activity by 4·3-fold as compared to normoxic control. Urotensin II siRNA almost completely attenuated the collagen I protein expression induced by hypoxia. Conclusions Hypoxia-induced urotensin II expression in cardiac fibroblast is mediated by angiotensin II and through ROS and JNK pathway. Urotensin II is a mediator of angiotensin II-induced cardiac fibrosis under hypoxia.

Original languageEnglish
Pages (from-to)17-26
Number of pages10
JournalEuropean Journal of Clinical Investigation
Issue number1
StatePublished - 01 2012


  • Cytokine
  • Fibrosis
  • Hypoxia
  • Reactive oxygen species
  • Urotensin II


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