TGF-β1-induced EMT activation via both Smad-dependent and MAPK signaling pathways in Cu-induced pulmonary fibrosis

被引:55
作者
Guo, Hongrui [1 ,2 ]
Jian, Zhijie [1 ]
Liu, Huan [1 ]
Cui, Hengmin [1 ,2 ,3 ]
Deng, Huidan [1 ,2 ]
Fang, Jing [1 ,2 ]
Zuo, Zhicai [1 ,2 ]
Wang, Xun [1 ,2 ]
Zhao, Ling [1 ,2 ]
Geng, Yi [1 ]
Ouyang, Ping [1 ]
Tang, Huaqiao [1 ]
机构
[1] Sichuan Agr Univ, Coll Vet Med, Chengdu 611130, Peoples R China
[2] Sichuan Agr Univ, Key Lab Anim Dis & Environm Hazards Sichuan Prov, Chengdu 611130, Peoples R China
[3] Sichuan Agr Univ, Key Lab Agr Informat Engn Sichuan Prov, Yaan 625014, Sichuan, Peoples R China
关键词
CuSO4; Lung; TGF-beta; 1; MAPKs; EMT; Mouse;
D O I
10.1016/j.taap.2021.115500
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Copper (Cu) is considered as an essential trace element for living organisms. However, over-exposure to Cu can lead to adverse health effects on human and animals. There are limited researches on pulmonary toxicity induced by Cu. Here, we found that copper sulfate (CuSO4)-treatment could induce pulmonary fibrosis with Masson staining and up-regulated protein and mRNA expression of Collagen I and alpha-Smooth Muscle Actin (alpha-SMA) in mice. Next, the mechanism underlying Cu-induced pulmonary fibrosis was explored, including transforming growth factor-beta 1 (TGF-beta 1)-mediated Smad pathway, mitogen-activated protein kinases (MAPKs) pathway and epithelial-mesenchymal transition (EMT). CuSO4 triggered pulmonary fibrosis by activation of the TGF-beta 1/Smad pathway, which was accomplished by increasing TGF-beta 1, p-Smad2 and p-Smad3 protein and mRNA expression levels. Also, up-regulated protein and mRNA expression of p-JNK, p-ERK, and p-p38 demonstrated that CuSO4 activated MAPKs pathways. Concurrently, EMT was activated by increasing vimentin and N-cadherin while decreasing E-cadherin protein and mRNA expression levels. Altogether, the abovementioned findings indicate that CuSO4 treatment may induce pulmonary fibrosis through the activation of EMT induced by TGF-beta 1/Smad pathway and MAPKs pathways, revealing the mechanism Cu-caused pulmonary toxicity.
引用
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页数:11
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