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

Min Ji Charng, Chieh Hsi Wu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

1. Tranilast, an antiallergic medication, is a very promising inhibitor of restenosis after balloon angioplasty. Tranilast can prevent the proliferation and migration of smooth muscle cells by activating the gene expression of p21, a strong cyclin/cyclin-dependent kinase (CDK) inhibitor, and by arresting cell growth at the G0/G1 phase. 2. The signaling pathway of Tranilast in regulating p21 is to our best interest and is elucidated in the present study. The major emphasis was weighted on exploring the regulatory effects of Tranilast on promoter activity of p21. 3. By serial deletion analysis, the sequence between -74 and -83 bp of the p21 promoter, previously identified as the transforming growth factor-β (TGF-β)-response element, was found sufficient, where as most of the promoter region 5′ to -111 bp was found unnecessary for the transcriptional activation of p21 by both TGF-β1 and Tranilast. 4. Tranilast was also found to induce phosphorylation of Smad2 (a cytoplasmic signaling molecule essential for mediating TGF-β signal transduction). Transfection of ΔkT/βRII, a truncated form of TGF-β type II receptor known to exert a dominant-negative effect on TGF-β signaling, was found to suppress the signaling of both Tranilast and TGF-β1 to a similar extent. 5. These results suggested that induction of p21 by Tranilast might be closely related to TGF-β signal transduction pathway.

Original languageEnglish
Pages (from-to)117-124
Number of pages8
JournalBritish Journal of Pharmacology
Volume147
Issue number1
DOIs
Publication statusPublished - Jan 2006
Externally publishedYes

Fingerprint

Transforming Growth Factor beta
Transforming Growth Factors
Transcriptional Activation
Signal Transduction
Anti-Allergic Agents
Growth Inhibitors
Cell Cycle Resting Phase
Cyclins
Balloon Angioplasty
Growth Factor Receptors
Cyclin-Dependent Kinases
tranilast
G1 Phase
Response Elements
Genetic Promoter Regions
Smooth Muscle Myocytes
Transfection
Phosphorylation
Gene Expression

Keywords

  • p21 induction
  • Restenosis
  • TGF-β response element
  • TGF-β signaling

ASJC Scopus subject areas

  • Pharmacology

Cite this

Transcriptional activation of p21 by Tranilast is mediated via transforming growth factor beta signal pathway. / Charng, Min Ji; Wu, Chieh Hsi.

In: British Journal of Pharmacology, Vol. 147, No. 1, 01.2006, p. 117-124.

Research output: Contribution to journalArticle

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