The molecular regulation of resistin expression in cultured vascular smooth muscle cells under hypoxia

Huei Fong Hung, Bao Wei Wang, Hang Chang, Kou-Gi Shyu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

OBJECTIVES: Resistin has a potential role in atherosclerosis because resistin produces proinflammatory effects in the vascular wall. However, the molecular mechanism of resistin increase in atherosclerosis remains unclear. Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells functions. We sought to investigate the molecular regulation of resistin expression under hypoxia in cultured vascular smooth muscle cells. METHODS: Vascular smooth muscle cells from thoracic aorta of adult Wistar rats were cultured and subjected to hypoxia at 2.5% oxygen in a hypoxic chamber. Western blot, real-time PCR, reactive oxygen species assay, and promoter activity were measured. RESULTS: Hypoxia significantly increased the resistin protein (3.5-fold, P <0.001) and mRNA (4.8-fold, P <0.001) expression as compared with the control cells. The specific extracellular signal-regulated kinase (ERK) inhibitor PD98059, antioxidant N-acetylcysteine, and ERK siRNA attenuated the induction of resistin protein by hypoxia. It increased the phosphorylated ERK protein expression (3.2-fold, P <0.001), whereas pretreatment with PD98059 and N-acetylcysteine significantly blocked the increase of phosphorylated ERK by hypoxia. It also increased the reactive oxygen species production (9.3-fold, P <0.001), and pretreatment with N-acetylcysteine significantly blocked the induction of reactive oxygen species by hypoxia. Hypoxia increased resistin promoter activity (5.1-fold, P <0.001), and the activity was abolished when nuclear factor of activating T cells in the promoter area was mutated. Pretreatment with PD98059 and N-acetylcysteine significantly attenuated the resistin promoter activity induced by hypoxia. CONCLUSION: Hypoxia increases the resistin expression in cultured rat vascular smooth muscle cells under hypoxia. The hypoxia-induced resistin is mediated through reactive oxygen species, ERK mitogen-activated protein (MAP) kinase and nuclear factor of activating T cells pathway.

Original languageEnglish
Pages (from-to)2349-2360
Number of pages12
JournalJournal of Hypertension
Volume26
Issue number12
DOIs
Publication statusPublished - Dec 2008

Fingerprint

Resistin
Cell Hypoxia
Vascular Smooth Muscle
Smooth Muscle Myocytes
Extracellular Signal-Regulated MAP Kinases
Acetylcysteine
Reactive Oxygen Species
TCF Transcription Factors
Atherosclerosis
Hypoxia
Proteins
Mitogen-Activated Protein Kinases
Thoracic Aorta
Small Interfering RNA
Blood Vessels
Wistar Rats
Real-Time Polymerase Chain Reaction
Antioxidants
Western Blotting

Keywords

  • Hypoxia
  • Resistin
  • Signal pathway
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

The molecular regulation of resistin expression in cultured vascular smooth muscle cells under hypoxia. / Hung, Huei Fong; Wang, Bao Wei; Chang, Hang; Shyu, Kou-Gi.

In: Journal of Hypertension, Vol. 26, No. 12, 12.2008, p. 2349-2360.

Research output: Contribution to journalArticle

Hung, Huei Fong ; Wang, Bao Wei ; Chang, Hang ; Shyu, Kou-Gi. / The molecular regulation of resistin expression in cultured vascular smooth muscle cells under hypoxia. In: Journal of Hypertension. 2008 ; Vol. 26, No. 12. pp. 2349-2360.
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abstract = "OBJECTIVES: Resistin has a potential role in atherosclerosis because resistin produces proinflammatory effects in the vascular wall. However, the molecular mechanism of resistin increase in atherosclerosis remains unclear. Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells functions. We sought to investigate the molecular regulation of resistin expression under hypoxia in cultured vascular smooth muscle cells. METHODS: Vascular smooth muscle cells from thoracic aorta of adult Wistar rats were cultured and subjected to hypoxia at 2.5{\%} oxygen in a hypoxic chamber. Western blot, real-time PCR, reactive oxygen species assay, and promoter activity were measured. RESULTS: Hypoxia significantly increased the resistin protein (3.5-fold, P <0.001) and mRNA (4.8-fold, P <0.001) expression as compared with the control cells. The specific extracellular signal-regulated kinase (ERK) inhibitor PD98059, antioxidant N-acetylcysteine, and ERK siRNA attenuated the induction of resistin protein by hypoxia. It increased the phosphorylated ERK protein expression (3.2-fold, P <0.001), whereas pretreatment with PD98059 and N-acetylcysteine significantly blocked the increase of phosphorylated ERK by hypoxia. It also increased the reactive oxygen species production (9.3-fold, P <0.001), and pretreatment with N-acetylcysteine significantly blocked the induction of reactive oxygen species by hypoxia. Hypoxia increased resistin promoter activity (5.1-fold, P <0.001), and the activity was abolished when nuclear factor of activating T cells in the promoter area was mutated. Pretreatment with PD98059 and N-acetylcysteine significantly attenuated the resistin promoter activity induced by hypoxia. CONCLUSION: Hypoxia increases the resistin expression in cultured rat vascular smooth muscle cells under hypoxia. The hypoxia-induced resistin is mediated through reactive oxygen species, ERK mitogen-activated protein (MAP) kinase and nuclear factor of activating T cells pathway.",
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N2 - OBJECTIVES: Resistin has a potential role in atherosclerosis because resistin produces proinflammatory effects in the vascular wall. However, the molecular mechanism of resistin increase in atherosclerosis remains unclear. Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells functions. We sought to investigate the molecular regulation of resistin expression under hypoxia in cultured vascular smooth muscle cells. METHODS: Vascular smooth muscle cells from thoracic aorta of adult Wistar rats were cultured and subjected to hypoxia at 2.5% oxygen in a hypoxic chamber. Western blot, real-time PCR, reactive oxygen species assay, and promoter activity were measured. RESULTS: Hypoxia significantly increased the resistin protein (3.5-fold, P <0.001) and mRNA (4.8-fold, P <0.001) expression as compared with the control cells. The specific extracellular signal-regulated kinase (ERK) inhibitor PD98059, antioxidant N-acetylcysteine, and ERK siRNA attenuated the induction of resistin protein by hypoxia. It increased the phosphorylated ERK protein expression (3.2-fold, P <0.001), whereas pretreatment with PD98059 and N-acetylcysteine significantly blocked the increase of phosphorylated ERK by hypoxia. It also increased the reactive oxygen species production (9.3-fold, P <0.001), and pretreatment with N-acetylcysteine significantly blocked the induction of reactive oxygen species by hypoxia. Hypoxia increased resistin promoter activity (5.1-fold, P <0.001), and the activity was abolished when nuclear factor of activating T cells in the promoter area was mutated. Pretreatment with PD98059 and N-acetylcysteine significantly attenuated the resistin promoter activity induced by hypoxia. CONCLUSION: Hypoxia increases the resistin expression in cultured rat vascular smooth muscle cells under hypoxia. The hypoxia-induced resistin is mediated through reactive oxygen species, ERK mitogen-activated protein (MAP) kinase and nuclear factor of activating T cells pathway.

AB - OBJECTIVES: Resistin has a potential role in atherosclerosis because resistin produces proinflammatory effects in the vascular wall. However, the molecular mechanism of resistin increase in atherosclerosis remains unclear. Hypoxia plays an important role in vascular remodeling and directly affects vascular smooth muscle cells functions. We sought to investigate the molecular regulation of resistin expression under hypoxia in cultured vascular smooth muscle cells. METHODS: Vascular smooth muscle cells from thoracic aorta of adult Wistar rats were cultured and subjected to hypoxia at 2.5% oxygen in a hypoxic chamber. Western blot, real-time PCR, reactive oxygen species assay, and promoter activity were measured. RESULTS: Hypoxia significantly increased the resistin protein (3.5-fold, P <0.001) and mRNA (4.8-fold, P <0.001) expression as compared with the control cells. The specific extracellular signal-regulated kinase (ERK) inhibitor PD98059, antioxidant N-acetylcysteine, and ERK siRNA attenuated the induction of resistin protein by hypoxia. It increased the phosphorylated ERK protein expression (3.2-fold, P <0.001), whereas pretreatment with PD98059 and N-acetylcysteine significantly blocked the increase of phosphorylated ERK by hypoxia. It also increased the reactive oxygen species production (9.3-fold, P <0.001), and pretreatment with N-acetylcysteine significantly blocked the induction of reactive oxygen species by hypoxia. Hypoxia increased resistin promoter activity (5.1-fold, P <0.001), and the activity was abolished when nuclear factor of activating T cells in the promoter area was mutated. Pretreatment with PD98059 and N-acetylcysteine significantly attenuated the resistin promoter activity induced by hypoxia. CONCLUSION: Hypoxia increases the resistin expression in cultured rat vascular smooth muscle cells under hypoxia. The hypoxia-induced resistin is mediated through reactive oxygen species, ERK mitogen-activated protein (MAP) kinase and nuclear factor of activating T cells pathway.

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