Curdione ameliorates bleomycin-induced pulmonary fibrosis by repressing TGF-β-induced fibroblast to myofibroblast differentiation

被引:77
作者
Liu, Peng [1 ]
Miao, Kang [1 ]
Zhang, Lei [1 ]
Mou, Yong [1 ]
Xu, Yongjian [1 ]
Xiong, Weining [1 ,2 ]
Yu, Jun [3 ]
Wang, Yi [1 ]
机构
[1] Huazhong Univ Sci & Technol, Dept Resp & Crit Care Med, Key Lab Pulm Dis,Tongji Hosp,Hlth Minist, Key Cite Natl Clin Res Ctr Resp Dis,Wuhan Clin Me, 1095 Jiefang Ave, Wuhan 430030, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Resp Med, Sch Med, 639 Zhizaoju Lu, Shanghai 201999, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Thorac Surg, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China
基金
中国国家自然科学基金;
关键词
IPF; Fibroblast; Myofibroblast; Curdione; TGF-beta; 1; PROTECTS MICE; PROLIFERATION;
D O I
10.1186/s12931-020-1300-y
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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.
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页数:10
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