Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02027 (Tranilast)
 205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N(3,4-dimethoxycinnamoyl) anthranilic acid (tranilast) prevents the synchronous upregulation of isoforms and receptors of the transforming growth factor (TGF)-beta system after arterial injury and reduces restenosis after human coronary angioplasty. However, the effects of tranilast and the importance of the TGF-beta system in stent restenosis, in which inward remodeling is unimportant but inflammatory cell stimulation of neointima formation is exaggerated, are uncertain. Boston minipigs, treated with tranilast or vehicle, were subjected to endoluminal stenting, and the expression of TGF-beta1 and TGF-beta3, the expression of their signaling receptors ALK-5 and TbetaR-II, leukocyte numbers around the stent struts, and neointima development were assessed over 28 days. Stenting greatly increased early (5-day) mRNA expression of the 2 TGF-beta isoforms and their receptors. Immunohistochemical localization later showed that their concentrations were greatest in regions adjacent to stent struts, where leukocytes and collagen deposition were prevalent. Tranilast suppressed these elevations in TGF-beta mRNAs and reduced their immunoreactive peptides detectable around stent struts. The accumulation of leukocytes and deposition of collagen in these regions was also greatly inhibited by tranilast. These effects were associated with a 48% reduction in maximal neointimal cross-sectional area and 43% reduction in mean neointimal cross-sectional area at 28 days (P<0.05). We conclude that tranilast suppresses neointima development after stenting, effects that can be at least partly attributed to its ability to attenuate the induction of the TGF-beta system and leukocyte accumulation around stent struts.
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PMID:Tranilast prevents activation of transforming growth factor-beta system, leukocyte accumulation, and neointimal growth in porcine coronary arteries after stenting. 1206 2

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. 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. By serial deletion analysis, the sequence between -74 and -83 bp of the p21 promoter, previously identified as the transforming growth factor-beta (TGF-beta)-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-beta1 and Tranilast. Tranilast was also found to induce phosphorylation of Smad2 (a cytoplasmic signaling molecule essential for mediating TGF-beta signal transduction). Transfection of DeltakTbetaRII, a truncated form of TGF-beta type II receptor known to exert a dominant-negative effect on TGF-beta signaling, was found to suppress the signaling of both Tranilast and TGF-beta1 to a similar extent. These results suggested that induction of p21 by Tranilast might be closely related to TGF-beta signal transduction pathway.
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PMID:Transcriptional activation of p21 by Tranilast is mediated via transforming growth factor beta signal pathway. 1628 27