Tranilast Inhibits Pulmonary Fibrosis by Suppressing TGFß/SMAD2 Pathway.
Drug Des Devel Ther
; 14: 4593-4603, 2020.
Article
in En
| MEDLINE
| ID: mdl-33149556
ABSTRACT
PURPOSE:
Idiopathic pulmonary fibrosis (IPF) is characterized by the accumulation of extracellular matrix (ECM) protein in the lungs. Transforming growth factor (TGF) ß-induced ECM protein synthesis contributes to the development of IPF. Tranilast, an anti-allergy drug, suppresses TGFß expression and inhibits interstitial renal fibrosis in animal models. However, the beneficial effects of tranilast or its mechanism as a therapy for pulmonary fibrosis have not been clarified.METHODS:
We investigated the in vitro effect of tranilast on ECM production and TGFß/SMAD2 pathway in TGFß2-stimulated A549 human alveolar epithelial cells, using quantitative polymerase chain reaction, Western blotting, and immunofluorescence. In vitro observations were validated in the lungs of a murine pulmonary fibrosis model, which we developed by intravenous injection of bleomycin.RESULTS:
Treatment with tranilast suppressed the expression of ECM proteins, such as fibronectin and type IV collagen, and attenuated SMAD2 phosphorylation in TGFß2-stimulated A549 cells. In addition, based on a wound healing assay in these cells, tranilast significantly inhibited cell motility, with foci formation that comprised of ECM proteins. Histological analyses revealed that the administration of tranilast significantly attenuated lung fibrosis in mice. Furthermore, tranilast treatment significantly reduced levels of TGFß, collagen, fibronectin, and phosphorylated SMAD2 in pulmonary fibrotic tissues in mice.CONCLUSION:
These findings suggest that tranilast inhibits pulmonary fibrosis by suppressing TGFß/SMAD2-mediated ECM protein production, presenting tranilast as a promising and novel anti-fibrotic agent for the treatment of IPF.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transforming Growth Factor beta
/
Smad2 Protein
/
Idiopathic Pulmonary Fibrosis
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Drug Des Devel Ther
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2020
Document type:
Article
Affiliation country:
Japan