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)

Tranilast (N(3,4-dimethoxycinnamoyl)anthranilic acid), an agent which in cell culture inhibits transforming growth factor-beta (TGF-beta) secretion and antagonises the effects of TGF-beta and platelet-derived growth factor (PDGF) on cell migration and proliferation, has been reported to reduce the incidence of restenosis after angioplasty in angiographically validated human clinical trials. We investigated in a rat model of balloon angioplasty whether tranilast's effects in vivo could be attributed to inhibition of expression of TGF-beta and/or its receptor types. Using a standardised reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we examined the effects of three doses of tranilast (25, 50 and 100 mg/kg) on the expression of two TGF-beta isoforms, the types I and II TGF-beta receptors and two putative TGF-beta responses, induction of integrins alpha(v) and beta3 mRNA, 2 h after oral administration and 26 h after vessel injury. Tranilast attenuated in a dose-dependent and reversible manner the injury-induced increases in mRNA levels encoding TGF-beta1, TGF-beta3, two type I TGF-beta receptors ALK-5 and ALK-2, and the type II receptor TbetaRII. At the highest dose mRNA levels encoding TGF-beta1 and TbetaRII were attenuated to levels approaching or below those observed in uninjured vessels. Messenger RNAs encoding TGF-beta3, ALK-5 and ALK-2 were all attenuated by between 70 and 74% (all P < 0.05). Tranilast also attenuated in a reversible manner the elevations in mRNA levels for integrins alpha(v) and beta3 observed after vessel injury, by 90 and 72%, respectively. We also investigated, in cultured smooth muscle cells derived from injured carotid arteries, the extent to which tranilast (300 mg/l) attenuated any increases in expression of type I and type II receptors stimulated by PDGF-BB and TGF-beta1, growth factors implicated in smooth muscle cell migration and proliferation in injured vessels. Increases in mRNA levels of the type I receptors ALK-5 and ALK-2 induced by PDGF-BB and TGF-beta1 were almost completely prevented by tranilast. Tranilast also prevented the PDGF-BB induced increases in TbetaRII but only partially inhibited the TGF-beta1 induced upregulation of TbetaRII. We conclude that tranilast can inhibit transcriptional mechanisms associated with the upregulation of TGF-beta and its receptor types in balloon catheter injured vessels. It is possible that these mechanisms contribute to its ability to reduce the frequency of restenosis after angioplasty.
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PMID:Inhibitory effects of tranilast on expression of transforming growth factor-beta isoforms and receptors in injured arteries. 962 70

The present study was conducted to assess the effect of Tranilast, a drug developed as anti-keloid and anti-hypertrophic scar agent, on the level of transforming growth factor- A1 (TGF- A1) mRNA, and on TGF- A1 secretion in Chang Conjunctiva cells. TGF- A1 mRNA was not detected in Chang Conjunctiva cells by Northern blot analysis, but reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the presence of TGF- A1 mRNA. Tranilast, whereas the drug had no effect on the levels of TGF- A1 mRNA and cellular protein, time- and dose-dependently inhibited TGF- A1 secretion from Chang Conjunctiva cells in the enzyme-linked immunosorbent assay (ELISA) analysis. TGF- A1 is suggested to cause fibroblast proliferation, that obstructs aqueous humor filtration route after glaucoma filtration surgery. Tranilast, potentially inhibiting TGF- A1 secretion, therefore, could be a promising drug to prevent from scarring after glaucoma filtration surgery.
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PMID:Tranilast inhibits TGF- A1 secretion without affecting its mRNA levels in conjunctival cells. 1178 98

Tranilast is an anti-allergic agent that blocks the release of chemical mediators, such as histamine and leukotrienes from mast cells, and has been reported to suppress keloid and hypertrophic scar formation. Since matrix metalloproteinases (MMPs) play an essential role in tissue remodelling, this study was undertaken to determine whether tranilast suppresses MMP production from neutrophils after lipopolysaccharide (LPS) stimulation in-vitro. Neutrophils from five healthy donors (1 x 10(5) cells/mL) were stimulated with 1.0 microg mL(-1) LPS in the presence or absence of various concentrations of tranilast for 24 h. MMP-7, MMP-8, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 levels in the culture supernatants were assayed by ELISA. In addition, the influence of tranilast on MMP mRNA expression and transcriptional factor activation in cells cultured for 12 h and 4 h was also evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Tranilast inhibited MMP and TIMP-1 production from neutrophils when cells were treated with the agent at more than 5.0 x 10(-5) M. It also suppressed MMP mRNA expression and transcriptional factor activation induced in neutrophils by LPS stimulation. The results suggest that tranilast inhibits the formation of keloid scarring through the suppression of factors such as MMPs and TIMP, which are essential for tissue remodelling, from inflammatory cells.
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PMID:Effect of tranilast on matrix metalloproteinase production from neutrophils in-vitro. 1639 68