Transcriptional activation of follistatin by Nrf2 protects pulmonary epithelial cells against silica nanoparticle-induced oxidative stress
Authors
Lin, ChenZhao, Xinyuan
Sun, Desen
Zhang, Lingda
Fang, Wenpan
Zhu, Tingjia
Wang, Qiang
Liu, Botao
Wei, Saisai
Chen, Guangdi
Xu, Zhengping
Gao, Xiangwei
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2016-02-16
Metadata
Show full item recordAbstract
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.Source
Sci Rep. 2016 Feb 16;6:21133. doi: 10.1038/srep21133. Link to article on publisher's siteDOI
10.1038/srep21133Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39941PubMed ID
26878911Related Resources
Link to Article in PubMedRights
Copyright © 2016, The Author(s).Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1038/srep21133