Copper Exposure Induces Epithelial-Mesenchymal Transition-Related Fibrotic Change via Autophagy and Increase Risk of Lung Fibrosis in Human

被引：13

作者：

Chiou, Hsin-Ying Clair ^{[1
,2
,3
]}

Wang, Chih-Wen ^{[4
,5
,6
]}

Chen, Szu-Chia ^{[5
,6
,7
]}

Tsai, Mei-Lan ^{[8
,9
]}

Lin, Ming-Hong ^{[10
,11
,12
]}

Hung, Chih-Hsing ^{[6
,13
,14
]}

Kuo, Chao-Hung ^{[5
,15
]}

机构：

[1] Kaohsiung Med Univ, Kaohsiung Municipal Siaogang Hosp, Teaching & Res Ctr, Kaohsiung 807, Taiwan

[2] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Kaohsiung 807, Taiwan

[3] Natl Chi Nan Univ, Dept Appl Chem, Nantou 540, Taiwan

[4] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Internal Med, Div Hepatobiliary, Kaohsiung 807, Taiwan

[5] Kaohsiung Med Univ, Kaohsiung Municipal Siaogang Hosp, Dept Internal Med, Kaohsiung 807, Taiwan

[6] Kaohsiung Med Univ, Res Ctr Environm Med, Kaohsiung 807, Taiwan

[7] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Internal Med, Div Nephrol, Kaohsiung 807, Taiwan

[8] Kaohsiung Med Univ, Grad Inst Med, Coll Med, Kaohsiung 807, Taiwan

[9] Kaohsiung Med Univ, Coll Med, Fac Pediat, Dept Pediat, Kaohsiung 807, Taiwan

[10] Kaohsiung Med Univ, Coll Med, Sch Med, Dept Microbiol & Immunol, Kaohsiung 807, Taiwan

[11] Kaohsiung Med Univ, Coll Med, Master Sci Program Trop Med, Kaohsiung 807, Taiwan

[12] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung 807, Taiwan

[13] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Pediat, Kaohsiung 807, Taiwan

[14] Kaohsiung Med Univ, Kaohsiung Municipal Siaogang Hosp, Dept Pediat, Kaohsiung 807, Taiwan

[15] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Internal Med, Div Gastroenterol, Kaohsiung 807, Taiwan

来源：

ANTIOXIDANTS | 2023年 / 12卷 / 02期

关键词：

copper; pulmonary fibrosis; epithelial-mesenchymal transition; flavonoid; autophagy; IDIOPATHIC PULMONARY-FIBROSIS; METALS; TOXICITY; URINE; BLOOD; IONS;

D O I：

10.3390/antiox12020532

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Copper is an essential trace element involved in several vital biological processes of the human body. However, excess exposure to copper caused by occupational hazards and environmental contamination, such as food, water, and air, damages human health. In this study, in vitro cell culture model and epidemiologic studies were conducted to evaluate the effect of copper on lung fibrosis. In vitro, treatment of CuSO4 in lung epithelial cells at 100 mu M consistently decreases cell viability in alveolar type (A549) and human bronchial epithelial (HBE) cells. CuSO4 promotes epithelial-mesenchymal transition (EMT) as shown by increased cell migration and increased EMT marker and fibrotic gene expressions. Besides, CuSO4 induced cell autophagy, with an increased LC3, PINK, and decreased p62 expression. Inhibition of ROS by N-acetylcysteine reversed the CuSO4-induced PINK1, LC3, and Snail expressions. Inhibition of autophagy by chloroquine reverses the CuSO4-induced EMT changes. Nature flavonoids, especially kaempferol, and fustin, were shown to inhibit Copper-induced EMT. In humans, a unit increase in urinary copper concentration was significantly associated with an increased risk of lung fibrotic changes (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.01-1.36, p = 0.038). These results indicated that Copper is a risk factor for lung fibrosis through activation of the ROS-autophagy-EMT pathway, which can be reversed by flavonoids.

引用

页数：17

共 45 条

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