Program in Molecular Medicine
Cell Biology | Genetics and Genomics | Nanomedicine
Silica nanoparticles (SiO2 NPs) cause oxidative stress in respiratory system. Meanwhile, human cells launch adaptive responses to overcome SiO2 NP toxicity. However, besides a few examples, the regulation of SiO2 NP-responsive proteins and their functions in SiO2 NP response remain largely unknown. In this study, we demonstrated that SiO2 NP induced the expression of follistatin (FST), a stress responsive gene, in mouse lung tissue as well as in human lung epithelial cells (A549). The levels of Ac-H3(K9/18) and H3K4me2, two active gene markers, at FST promoter region were significantly increased during SiO2 NP treatment. The induction of FST transcription was mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2), as evidenced by the decreased FST expression in Nrf2-deficient cells and the direct binding of Nrf2 to FST promoter region. Down-regulation of FST promoted SiO2 NP-induced apoptosis both in cultured cells and in mouse lung tissue. Furthermore, knockdown of FST increased while overexpression of FST decreased the expression level of NADPH oxidase 1 (NOX1) and NOX5 as well as the production of cellular reactive oxygen species (ROS). Taken together, these findings demonstrated a protective role of FST in SiO2 NP-induced oxidative stress and shed light on the interaction between SiO2 NPs and biological systems.
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Copyright © 2016, The Author(s).
DOI of Published Version
Sci Rep. 2016 Feb 16;6:21133. doi: 10.1038/srep21133. Link to article on publisher's site
Lin, Chen; Zhao, Xinyuan; Sun, Desen; Zhang, Lingda; Fang, Wenpan; Zhu, Tingjia; Wang, Qiang; Liu, Botao; Wei, Saisai; Chen, Guangdi; Xu, Zhengping; and Gao, Xiangwei, "Transcriptional activation of follistatin by Nrf2 protects pulmonary epithelial cells against silica nanoparticle-induced oxidative stress" (2016). Open Access Articles. 2750.
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