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

来源：

RESPIRATORY RESEARCH | 2020年 / 21卷 / 01期

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.

引用

页数：10

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