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

被引：95

作者：

Zhou, Wencheng ^{[1
]}

Mo, Xiaoting ^{[1
]}

Cui, Wenhui ^{[1
,2
]}

Zhang, Zhihui ^{[3
]}

Li, Delin ^{[4
]}

Li, Liucheng ^{[3
]}

Xu, Liang ^{[3
]}

Yao, Hongwei ^{[1
]}

Gao, Jian ^{[2
]}

机构：

[1] Anhui Med Univ, Sch Pharm, Hefei 230032, Anhui, Peoples R China

[2] Dalian Med Univ, Hosp 2, Dalian 116023, Peoples R China

[3] Anhui Med Univ, Affiliated Hosp 1, Hefei 230022, Peoples R China

[4] Anhui Univ Chinese Med, Hefei 230038, Anhui, Peoples R China

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

中国国家自然科学基金;

关键词：

TRANSCRIPTION FACTOR; PROTECTS; PATHOGENESIS; OXYGENASE-1; MECHANISMS; INVASION; PATHWAY;

D O I：

10.1038/srep38646

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 beta 1 (TGF-beta 1)-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-beta 1-induced EMT, accompanied by the down-regulation of snail. Inversely, silencing Nrf2 by siRNA enhanced TGF-beta 1-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.

引用

页数：10

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