α-tocopherol induces expression of connective tissue growth factor and antagonizes tumor necrosis factor-α-mediated downregulation in human smooth muscle cells

Luis Villacorta, Aurélio V. Graça-Souza, Roberta Ricciarelli, Jean Marc Zingg, Angelo Azzi

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

The effect of α-tocopherol treatment on gene expression in human aortic vascular smooth muscle cells was analyzed by gene expression arrays. The expression of the connective tissue growth factor (CTGF) gene was induced by α-tocopherol 1.8-fold in gene array experiments, and similar results were also obtained by RT-PCR (1.7-fold) and at the protein level (1.4-fold). The antioxidants β-tocopherol and N-acetylcysteine did not induce CTGF gene expression, suggesting a nonantioxidant mechanism for α-tocopherol action. Protein kinase C (PKC) inhibition by α-tocopherol has been previously described. However, PKC downregulation did not prevent CTGF induction by α-tocopherol, and inhibition of PKC activity with several inhibitors did not increase its expression, suggesting an alternative pathway for the α-tocopherol effect. On the other hand, tumor necrosis factor-α reduced the expression of CTGF, an effect that was reversed by antioxidants. The data suggest that tumor necrosis factor-α inhibition of CTGF gene expression is prevented in an antioxidant-sensitive process and that α-tocopherol increases CTGF expression by a PKC-independent, nonantioxidant mechanism. Because CTGF stimulates the synthesis of extracellular matrix, the normalization of CTGF gene expression by α-tocopherol may accelerate wound repair and tissue regeneration during atherosclerosis.

Original languageEnglish (US)
Pages (from-to)104-110
Number of pages7
JournalCirculation research
Volume92
Issue number1
DOIs
StatePublished - Jan 10 2003
Externally publishedYes

Keywords

  • α-tocopherol
  • Connective tissue growth factor
  • Okadaic acid
  • Protein kinase C
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'α-tocopherol induces expression of connective tissue growth factor and antagonizes tumor necrosis factor-α-mediated downregulation in human smooth muscle cells'. Together they form a unique fingerprint.

Cite this