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Respiratory exposure to nano‐TiO 2 induces pulmonary toxicity in mice involving reactive free radical‐activated TGF‐β/Smad/p38MAPK/Wnt pathways
Author(s) -
Zhou Yingjun,
Ji Jianhui,
Ji Li,
Wang Ling,
Hong Fashui
Publication year - 2019
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.36762
Subject(s) - smad , pulmonary fibrosis , wnt signaling pathway , transforming growth factor , fibrosis , signal transduction , cancer research , biology , microbiology and biotechnology , chemistry , medicine
Numerous studies have shown that lung injury can be caused by respiratory exposure to nanoparticulate titanium dioxide (nano‐TiO 2 ), but whether pulmonary inflammation and fibrosis are related to the activation of the TGF‐β/Smad/p38MAPK/Wnt pathways remains unclear. In this study, mice were administrated nano‐TiO 2 by nasal instillation for nine consecutive months, and the molecular mechanisms of nano‐TiO 2 on the pulmonary toxicity of mice were examined. The findings suggested that nano‐TiO 2 caused pneumonia and pulmonary fibrosis. Furthermore, the results also showed that an overproduction of reactive free radicals occurred in mouse lungs, and that the expression of TGF‐β/p38MAPK/Wnt pathway‐related factors, including hypoxia‐inducible factor 1α (HIF‐1α), transforming growth factor‐β1 (TGF‐β1), phosphorylated p38 mitogen activated protein kinases (p‐p38MAPK), small mothers against decapentaplegic homolog 2 (Smad2), extracellular matrix (ECM), Wingless/Integrated 3 (Wnt3), Wingless/Integrated 4 (Wnt4), integrin‐linked kinase (ILK), β‐catenin, nuclear factor‐κB (NF‐κB), α‐smooth muscle actin (α‐SMA), c‐Myc, Type I collage (collagen I), and Type collage III (collagen III) were remarkably elevated, while phosphorylated glycogen synthase kinase‐3β (p‐GSK‐3β) expression was decreased. Those data implied that the pulmonary inflammation and fibrosis caused by nano‐TiO 2 exposure may be involved in reactive free radical‐mediated activation of the TGF‐β/Smad/p38MAPK/Wnt pathways.