Curdione ameliorates bleomycin-induced pulmonary fibrosis by repressing TGF-β-induced fibroblast to myofibroblast differentiation
Curdione ameliorates bleomycin-induced pulmonary fibrosis by repressing TGF-β-induced fibroblast to myofibroblast differentiation
复制标题
Curdione 通过抑制 TGF-β 诱导的成纤维细胞向肌成纤维细胞分化改善博莱霉素诱导的肺纤维化
DOI：
10.1186/s12931-020-1300-y
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发表时间：
2020-02-19
影响因子：
5.8
通讯作者：
Wang, Yi
中科院分区：
文献类型：
--
作者：
Liu, Peng;Miao, Kang;Wang, Yi
Background Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible disease characterized by excessive fibroblast to myofibroblast differentiation with limited therapeutic options. Curdione, a sesquiterpene compound extracted from the essential oil of Curcuma aromatica Salisb, has anti-inflammatory and anti-tumor effects. However, the role of curdione in IPF is still unclear. Methods The effects of curdione were evaluated in a bleomycin (BLM)-induced pulmonary fibrosis mouse model. C57BL/6 mice were treated with BLM on day 0 by intratracheal injection and intraperitoneal administered curdione or vehicle. In vitro study, expression of fibrotic protein was examined and the transforming growth factor (TGF)-beta-related signaling was evaluated in human pulmonary fibroblasts (HPFs) treated with curdione following TGF-beta 1 stimulation. Results Histological and immunofluorescent examination showed that curdione alleviated BLM-induced lung injury and fibrosis. Specifically, curdione significantly attenuated fibroblast to myofibroblast differentiation in the lung in BLM induced mice. Furthermore, curdione also decreased TGF-beta 1 induced fibroblast to myofibroblast differentiation in vitro, as evidenced by low expression of alpha-SMA, collagen 1 and fibronectin in a dose dependent manner. Mechanistically, curdione suppressed the phosphorylation of Smad3 following TGF-beta 1 treatment, thereby inhibiting fibroblast differentiation. Conclusions Overall, curdione exerted therapeutic effects against pulmonary fibrosis via attenuating fibroblast to myofibroblast differentiation. As curdione had been shown to be safe and well-tolerated in BLM-induced mouse model, curdione might be useful for developing novel therapeutics for IPF.
