論文 - 詳細
| RRC ID | 65123 |
|---|---|
| 著者 | Yamazaki R, Kasuya Y, Fujita T, Umezawa H, Yanagihara M, Nakamura H, Yoshino I, Tatsumi K, Murayama T. |
| タイトル | Antifibrotic effects of cyclosporine A on TGF-β1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1α. |
| ジャーナル | FASEB J |
| Abstract |
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-β1 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 α-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-β1-induced FMD via degradation of hypoxia-inducible factor-1α (HIF-1α). In addition, in primary myofibroblast-like cells that were obtained from a patient with pulmonary fibrosis, treatment with CsA and an HIF-1α inhibitor (HIFi) decreased the expression levels of α-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-1α and that the CsA-HIF-1α 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-β1-treated lung fibroblasts and lungs from bleomycin-treated mice: role of hypoxia-inducible factor-1α. |
| 巻・号 | 31(8) |
| ページ | 3359-3371 |
| 公開日 | 2017-8-1 |
| DOI | 10.1096/fj.201601357R |
| PII | fj.201601357R |
| PMID | 28446589 |
| MeSH | Animals Bleomycin / toxicity Cell Line Cyclosporine / pharmacology* Fibroblasts / drug effects* Humans Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors Hypoxia-Inducible Factor 1, alpha Subunit / genetics Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Immunosuppressive Agents / pharmacology* Lung / cytology Lung / drug effects Male Mice Mice, Inbred C57BL Pulmonary Fibrosis / chemically induced* Pulmonary Fibrosis / metabolism Transforming Growth Factor beta1 / pharmacology* |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | WI-38(RCB0702) |