| First Author | Yamazaki R | Year | 2017 |
| Journal | FASEB J | Volume | 31 |
| Issue | 8 | Pages | 3359-3371 |
| PubMed ID | 28446589 | Mgi Jnum | J:247649 |
| Mgi Id | MGI:5926505 | Doi | 10.1096/fj.201601357R |
| Citation | Yamazaki R, et al. (2017) Antifibrotic effects of cyclosporine A on TGF-beta1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1alpha. FASEB J 31(8):3359-3371 |
| abstractText | Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder that is characterized by aberrant tissue remodeling and the formation of fibroblastic foci that are composed of fibrogenic myofibroblasts. TGF-beta1 is one of the factors that are responsible for fibrosis as it promotes fibroblast to myofibroblast differentiation (FMD) and is associated with up-regulation of alpha-smooth muscle actin. Therefore, inhibition of FMD may represent an effective strategy for the treatment of IPF. Here, we describe the treatment of human lung fibroblasts (WI-38 and HFL-1 cells) with cyclosporine A (CsA), which reduces TGF-beta1-induced FMD via degradation of hypoxia-inducible factor-1alpha (HIF-1alpha). In addition, in primary myofibroblast-like cells that were obtained from a patient with pulmonary fibrosis, treatment with CsA and an HIF-1alpha inhibitor (HIFi) decreased the expression levels of alpha-smooth muscle actin and fibronectin, which indicated that CsA and HIFi promote dedifferentiation of myofibroblasts. In mice intratracheally administered CsA or HIFi at an early fibrotic stage [7, 8, and 9 d postinstillation (dpi) of bleomycin], marked alleviation of lung fibrosis was observed at 14 dpi. These results suggest that CsA exhibits antifibrotic effects by degrading HIF-1alpha and that the CsA-HIF-1alpha axis provides new insights into therapeutic options for the treatment of IPF.-Yamazaki, R., Kasuya, Y., Fujita, T., Umezawa, H., Yanagihara, M., Nakamura, H., Yoshino, I., Tatsumi, K., Murayama, T. Antifibrotic effects of cyclosporine A on TGF-beta1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1alpha. |
