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Updated: Aug 9, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

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Transcriptional activation of p21 by Tranilast is mediated via transforming growth factor beta signal pathway

Min-Ji Charng1, Chieh-Hsi Wu

  • 1Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan.

British Journal of Pharmacology
|November 15, 2005
PubMed

Insights

Tranilast inhibits restenosis by activating p21 gene expression, halting smooth muscle cell growth. This study reveals Tranilast utilizes the transforming growth factor-beta (TGF-beta) signaling pathway to achieve this effect.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Pharmacology

Background:

  • Restenosis after balloon angioplasty remains a clinical challenge.
  • Tranilast, an antiallergic drug, shows potential in inhibiting restenosis.
  • Smooth muscle cell proliferation and migration are key factors in restenosis development.

Purpose of the Study:

  • To elucidate the signaling pathway of Tranilast in regulating p21 expression.
  • To investigate the effects of Tranilast on p21 promoter activity.
  • To understand Tranilast's mechanism in preventing smooth muscle cell proliferation.

Main Methods:

  • Serial deletion analysis of the p21 promoter region.
  • Assessing transcriptional activation by Tranilast and TGF-beta1.
  • Inducing phosphorylation of Smad2.
  • Transfection with dominant-negative TGF-beta type II receptor (DeltakTbetaRII).

Main Results:

  • A specific region (-74 to -83 bp) of the p21 promoter is crucial for transcriptional activation by Tranilast and TGF-beta1.
  • Tranilast induces phosphorylation of Smad2, a key TGF-beta signaling molecule.
  • Inhibition of TGF-beta signaling pathway suppressed Tranilast's effect on p21.

Conclusions:

  • Tranilast activates p21 gene expression, leading to cell cycle arrest at G0/G1 phase.
  • The mechanism of Tranilast involves the transforming growth factor-beta (TGF-beta) signal transduction pathway.
  • Tranilast shows promise as a therapeutic agent for preventing restenosis.

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