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

• Published in: Scientific reports Vol. 6; no. 1; p. 38646
• Main Authors: Zhou, Wencheng, Mo, Xiaoting, Cui, Wenhui, Zhang, Zhihui, Li, Delin, Li, Liucheng, Xu, Liang, Yao, Hongwei, Gao, Jian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.12.2016; Nature Publishing Group
• Subjects: 13; 13/1; 13/109; 13/51; 13/89; 13/95; 631/80/79/1902; 631/80/86; 82; 82/1; 82/29; 82/51; 82/80; Alveoli; Animals; Bleomycin; Cell Line; Epithelial cells; Epithelial-Mesenchymal Transition - drug effects; Fibrosis; Gene Silencing - drug effects; Humanities and Social Sciences; Lung diseases; Mesenchyme; Mice; Models, Biological; multidisciplinary; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - metabolism; Pulmonary Alveoli - pathology; Pulmonary fibrosis; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Rats; Rodents; Science; siRNA; Snail Family Transcription Factors - metabolism; Sulforaphane; Transforming growth factor; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor-b1
• DOI: 10.1038/srep38646
• ISSN: 2045-2322

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.