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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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
Volume42
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Fibroblasts
Angiotensin II
Reactive Oxygen Species
Losartan
Acetylcysteine
Small Interfering RNA
urotensin II
Hypoxia
Proteins
Collagen
Fibrosis
Angiotensin Receptor Antagonists
MAP Kinase Signaling System
Rats

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Biochemistry
  • Biochemistry

Cite this

Angiotensin II mediates urotensin II expression by hypoxia in cultured cardiac fibroblast. / Shyu, Kou Gi; Wang, Bao Wei; Chen, Wei Jan; Kuan, Peiliang; Lin, Chiu Mei.

In: European Journal of Clinical Investigation, Vol. 42, No. 1, 01.2012, p. 17-26.

Research output: Contribution to journalArticle

Shyu, Kou Gi ; Wang, Bao Wei ; Chen, Wei Jan ; Kuan, Peiliang ; Lin, Chiu Mei. / Angiotensin II mediates urotensin II expression by hypoxia in cultured cardiac fibroblast. In: European Journal of Clinical Investigation. 2012 ; Vol. 42, No. 1. pp. 17-26.
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N2 - 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.

AB - 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.

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