title: Epithelial-mesenchymal transition involved in pulmonary fibrosis induced by multi-walled carbon nanotubes via TGF-beta/Smad signaling pathway.
abstract: Multi-walled carbon nanotubes (MWCNT) are a typical nanomaterial with a wide spectrum of commercial applications. Inhalation exposure to MWCNT has been linked with lung fibrosis and mesothelioma-like lesions commonly seen with asbestos. In this study, we examined the pulmonary fibrosis response to different length of MWCNT including short MWCNT (S-MWCNT, length=350-700nm) and long MWCNT (L-MWCNT, length=5-15μm) and investigated whether the epithelial-mesenchymal transition (EMT) occurred during MWCNT-induced pulmonary fibrosis. C57Bl/6J male mice were intratracheally instilled with S-MWCNT or L-WCNT by a single dose of 60μg per mouse, and the progress of pulmonary fibrosis was evaluated at 7, 28 and 56 days post-exposure. The in vivo data showed that only L-MWCNT increased collagen deposition and pulmonary fibrosis significantly, and approximately 20% of pro-surfactant protein-C positive epithelial cells transdifferentiated to fibroblasts at 56 days, suggesting the occurrence of EMT. In order to understand the mechanism, we used human pulmonary epithelial cell line A549 to investigate the role of TGF-β/p-Smad2 signaling pathway in EMT. Our results showed that L-MWCNT downregulated E-cadherin and upregulated α-smooth muscle actin (α-SMA) protein expression in A549 cells. Taken together, both in vivo and in vitro study demonstrated that respiratory exposure to MWCNT induced length dependent pulmonary fibrosis and epithelial-derived fibroblasts via TGF-β/Smad pathway.
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Rd, Beijing 100191, China. Electronic address: chentian@bjmu.edu.cn.
authors: Tian
authors: T
authors: Chen
authors: Department of Applied Chemistry, China Agricultural University, No. 2 Yuanmingyuan West Rd, Beijing 100194, China. Electronic address: niehaiyu342@163.com.
authors: Haiyu
authors: H
authors: Nie
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Rd, Beijing 100191, China. Electronic address: gaoxin0_0@163.com.
authors: Xin
authors: X
authors: Gao
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Rd, Beijing 100191, China. Electronic address: goodboylinlin@163.com.
authors: Jinglin
authors: J
authors: Yang
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Rd, Beijing 100191, China. Electronic address: puji328@bjmu.edu.cn.
authors: Ji
authors: J
authors: Pu
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Rd, Beijing 100191, China. Electronic address: czjczj01@163.com.
authors: Zhangjian
authors: Z
authors: Chen
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Rd, Beijing 100191, China. Electronic address: cuixiaoxing@gmail.com.
authors: Xiaoxing
authors: X
authors: Cui
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Rd, Beijing 100191, China. Electronic address: wangyun@bjmu.edu.cn.
authors: Yun
authors: Y
authors: Wang
authors: Institute of Nanochemistry and Nanobiology, Shanghai University, No. 99 Shangda Rd, Shanghai 200444, China. Electronic address: hwang@shu.edu.cn.
authors: Haifang
authors: H
authors: Wang
authors: Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, No. 38 Xueyuan Rd, Beijing 100191, China. Electronic address: jiaguangjia@bjmu.edu.cn.
authors: Guang
authors: G
authors: Jia
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D037742:Nanotubes, Carbon; D010316:Particle Size; D010766:Phosphorylation; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015703:Antigens, CD; D015415:Biomarkers; C513384:CDH1 protein, human; D015820:Cadherins; D037742:Nanotubes, Carbon; C497782:SMAD2 protein, human; D051899:Smad2 Protein; C497784:Smad2 protein, rat; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D003094:Collagen
keywords: Epithelial–mesenchymal transition; MWCNT; Pulmonary fibrosis; Smad; TGF-β