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Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis

Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system,...

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Autores principales: Zhou, Wencheng, Mo, Xiaoting, Cui, Wenhui, Zhang, Zhihui, Li, Delin, Li, Liucheng, Xu, Liang, Yao, Hongwei, Gao, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159829/
https://www.ncbi.nlm.nih.gov/pubmed/27982105
http://dx.doi.org/10.1038/srep38646
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author Zhou, Wencheng
Mo, Xiaoting
Cui, Wenhui
Zhang, Zhihui
Li, Delin
Li, Liucheng
Xu, Liang
Yao, Hongwei
Gao, Jian
author_facet Zhou, Wencheng
Mo, Xiaoting
Cui, Wenhui
Zhang, Zhihui
Li, Delin
Li, Liucheng
Xu, Liang
Yao, Hongwei
Gao, Jian
author_sort Zhou, Wencheng
collection PubMed
description Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail thereby modulating the development of PF. Here, bleomycin (BLM) was intratracheally injected into both Nrf2-knockout (Nrf2(−/−)) and wild-type mice to compare the development of PF. Rat type II alveolar epithelial cells (RLE-6TN) were treated with a specific Nrf2 activator sulforaphane, or transfected with Nrf2 and snail siRNAs to determine their effects on transforming growth factor β1 (TGF-β1)-induced EMT. We found that BLM-induced EMT and lung fibrosis were more severe in Nrf2(−/−) mice compared to wild-type mice. In vitro, sulforaphane treatment attenuated TGF-β1-induced EMT, accompanied by the down-regulation of snail. Inversely, silencing Nrf2 by siRNA enhanced TGF-β1-induced EMT along with increased expression of snail. Interestingly, when snail was silenced by siRNA, sulforaphane treatment was unable to reduce the progression of EMT in RLE-6TN cells. These findings suggest that Nrf2 attenuates EMT and fibrosis process by regulating the expression of snail in PF.
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spelling pubmed-51598292016-12-21 Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis Zhou, Wencheng Mo, Xiaoting Cui, Wenhui Zhang, Zhihui Li, Delin Li, Liucheng Xu, Liang Yao, Hongwei Gao, Jian Sci Rep Article Epithelial-mesenchymal transition (EMT) is a phenotype conversion that plays a critical role in the development of pulmonary fibrosis (PF). It is known that snail could regulate the progression of EMT. Nuclear factor erythroid 2 related factor 2 (Nrf2), a key regulator of antioxidant defense system, protects cells against oxidative stress. However, it is not known whether Nrf2 regulates snail thereby modulating the development of PF. Here, bleomycin (BLM) was intratracheally injected into both Nrf2-knockout (Nrf2(−/−)) and wild-type mice to compare the development of PF. Rat type II alveolar epithelial cells (RLE-6TN) were treated with a specific Nrf2 activator sulforaphane, or transfected with Nrf2 and snail siRNAs to determine their effects on transforming growth factor β1 (TGF-β1)-induced EMT. We found that BLM-induced EMT and lung fibrosis were more severe in Nrf2(−/−) mice compared to wild-type mice. In vitro, sulforaphane treatment attenuated TGF-β1-induced EMT, accompanied by the down-regulation of snail. Inversely, silencing Nrf2 by siRNA enhanced TGF-β1-induced EMT along with increased expression of snail. Interestingly, when snail was silenced by siRNA, sulforaphane treatment was unable to reduce the progression of EMT in RLE-6TN cells. These findings suggest that Nrf2 attenuates EMT and fibrosis process by regulating the expression of snail in PF. Nature Publishing Group 2016-12-16 /pmc/articles/PMC5159829/ /pubmed/27982105 http://dx.doi.org/10.1038/srep38646 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhou, Wencheng
Mo, Xiaoting
Cui, Wenhui
Zhang, Zhihui
Li, Delin
Li, Liucheng
Xu, Liang
Yao, Hongwei
Gao, Jian
Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
title Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
title_full Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
title_fullStr Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
title_full_unstemmed Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
title_short Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
title_sort nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5159829/
https://www.ncbi.nlm.nih.gov/pubmed/27982105
http://dx.doi.org/10.1038/srep38646
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