RT Journal Article
SR Electronic
T1 Tranilast inhibits pulmonary fibrosis by suppressing TGFβ-mediated extracellular matrix protein production
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2330
VO 42
IS Suppl 57
A1 Motoyasu Kato
A1 Fumiyuki Takahashi
A1 Tadashi Sato
A1 Fariz Nurwidya
A1 Isao Kobayashi
A1 Yoshito Hoshika
A1 Akiko Murakami
A1 Ryo Ko
A1 Shigehiro Yagishita
A1 Masakata Yoshioka
A1 Naoko Shimada
A1 Yasuko Yoshioka
A1 Motomi Takahashi
A1 Hideyuki Saya
A1 Kazuhisa Takahashi
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P2330.abstract
AB [Background]Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disorder of unknown etiology, and is characterized by accumulation of extracellular matrix (ECM) protein such as fibronectin and collagen in the lungs. TGFβ-mediated epithelial-mesenchymal transition (EMT) of alveolar epithelial cells may contribute to the pathogenesis of IPF. On the other hand, tranilast, anti-allergic drug, is capable of suppressing TGFβ, and is reported to inhibit interstitial renal fibrosis in murine model.[Materials and Methods]We investigated an effect of tranilast on TGFβ-induced EMT in A549 human alveolar epithelial cells in vitro. To evaluate the efficacy of tranilast on lung fibrosis in vivo, we developed a mouse model for pulmonary fibrosis by intravenous injection of bleomycin (BLM). Tranilast were administered by oral gavage, and mice were sacrificed on day 22.[Result]Treatment with TGFβ induced EMT in A549 cells in vitro, and expression of mesenchymal proteins including fibronectin and type IV collagen were significantly suppressed by the administration of tranilast. Furthermore, treatment with tranilast significantly attenuated BLM-induced lung fibrosis in mice in vivo. The collagen content of the lungs was significantly lower in mice treated with tranilast as compared with that in control mice.[Conclusion]These findings suggest that tranilast inhibits pulmonary fibrosis by suppressing TGF β-mediated ECM protein production from mesenchymal cells. Tranilast may be promising and novel anti-fibrotic agent for the prevention of IPF.