RGD Reference Report - Inhibitory effects of tranilast on expression of transforming growth factor-beta isoforms and receptors in injured arteries. - Rat Genome Database

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Inhibitory effects of tranilast on expression of transforming growth factor-beta isoforms and receptors in injured arteries.

Authors: Ward, M R  Sasahara, T  Agrotis, A  Dilley, R J  Jennings, G L  Bobik, A 
Citation: Ward MR, etal., Atherosclerosis. 1998 Apr;137(2):267-75. doi: 10.1016/s0021-9150(97)00275-x.
RGD ID: 329845558
Pubmed: PMID:9622270   (View Abstract at PubMed)
DOI: DOI:10.1016/s0021-9150(97)00275-x   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Carotid Artery Injuries  ISOAcvr1 (Rattus norvegicus)329845558; 329845558mRNA:increased expression:carotic artery (rat)RGD 
Carotid Artery Injuries  IEP 329845558; 329845558; 329845558; 329845558; 329845558; 329845558; 329845558mRNA:increased expression:carotic artery (rat)RGD 
Carotid Artery Injuries  ISOItgav (Rattus norvegicus)329845558; 329845558mRNA:increased expression:carotic artery (rat)RGD 
Carotid Artery Injuries  ISOItgb3 (Rattus norvegicus)329845558; 329845558mRNA:increased expression:carotic artery (rat)RGD 
Carotid Artery Injuries  ISOTgfb1 (Rattus norvegicus)329845558; 329845558mRNA:increased expression:carotic artery (rat)RGD 
Carotid Artery Injuries  ISOTgfb3 (Rattus norvegicus)329845558; 329845558mRNA:increased expression:carotic artery (rat)RGD 
Carotid Artery Injuries  ISOTgfbr1 (Rattus norvegicus)329845558; 329845558mRNA:increased expression:carotic artery (rat)RGD 
Carotid Artery Injuries  ISOTgfbr2 (Rattus norvegicus)329845558; 329845558mRNA:increased expression:carotic artery (rat)RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
tranilast affects expression ISOAcvr1 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [TGF-b1 increases mRNA expression in rat carotid artery smooth muscle cell culture]RGD 
tranilast multiple interactionsISOAcvr1 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [PDGF-BB increases mRNA expression in rat carotid artery smooth muscle cell culture]RGD 
tranilast decreases expression ISOAcvr1 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [balloon angioplasty increases mRNA expression in rat carotid artery]RGD 
tranilast affects expression EXP 329845558; 329845558; 329845558tranilast inhibits the reaction [TGF-b1 increases mRNA expression in rat carotid artery smooth muscle cell culture]RGD 
tranilast multiple interactionsEXP 329845558; 329845558; 329845558tranilast inhibits the reaction [PDGF-BB increases mRNA expression in rat carotid artery smooth muscle cell culture]RGD 
tranilast decreases expression EXP 329845558; 329845558; 329845558; 329845558; 329845558; 329845558; 329845558tranilast inhibits the reaction [balloon angioplasty increases mRNA expression in rat carotid artery]RGD 
tranilast decreases expression ISOItgav (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [balloon angioplasty increases mRNA expression in rat carotid artery]RGD 
tranilast decreases expression ISOItgb3 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [balloon angioplasty increases mRNA expression in rat carotid artery]RGD 
tranilast decreases expression ISOTgfb1 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [balloon angioplasty increases mRNA expression in rat carotid artery]RGD 
tranilast decreases expression ISOTgfb3 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [balloon angioplasty increases mRNA expression in rat carotid artery]RGD 
tranilast affects expression ISOTgfbr1 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [TGF-b1 increases mRNA expression in rat carotid artery smooth muscle cell culture]RGD 
tranilast multiple interactionsISOTgfbr1 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [PDGF-BB increases mRNA expression in rat carotid artery smooth muscle cell culture]RGD 
tranilast decreases expression ISOTgfbr1 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [balloon angioplasty increases mRNA expression in rat carotid artery]RGD 
tranilast affects expression ISOTgfbr2 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [TGF-b1 increases mRNA expression in rat carotid artery smooth muscle cell culture]RGD 
tranilast multiple interactionsISOTgfbr2 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [PDGF-BB increases mRNA expression in rat carotid artery smooth muscle cell culture]RGD 
tranilast decreases expression ISOTgfbr2 (Rattus norvegicus)329845558; 329845558tranilast inhibits the reaction [balloon angioplasty increases mRNA expression in rat carotid artery]RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acvr1  (activin A receptor type 1)
Itgav  (integrin subunit alpha V)
Itgb3  (integrin subunit beta 3)
Tgfb1  (transforming growth factor, beta 1)
Tgfb3  (transforming growth factor, beta 3)
Tgfbr1  (transforming growth factor, beta receptor 1)
Tgfbr2  (transforming growth factor, beta receptor 2)

Genes (Mus musculus)
Acvr1  (activin A receptor, type 1)
Itgav  (integrin alpha V)
Itgb3  (integrin beta 3)
Tgfb1  (transforming growth factor, beta 1)
Tgfb3  (transforming growth factor, beta 3)
Tgfbr1  (transforming growth factor, beta receptor I)
Tgfbr2  (transforming growth factor, beta receptor II)

Genes (Homo sapiens)
ACVR1  (activin A receptor type 1)
ITGAV  (integrin subunit alpha V)
ITGB3  (integrin subunit beta 3)
TGFB1  (transforming growth factor beta 1)
TGFB3  (transforming growth factor beta 3)
TGFBR1  (transforming growth factor beta receptor 1)
TGFBR2  (transforming growth factor beta receptor 2)


Additional Information