title: Nrf2 inhibits epithelial-mesenchymal transition by suppressing snail expression during pulmonary fibrosis.
abstract: 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.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Mo
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, Anhui, 230032, China.|The Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Cui
authors.affiliation: The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Anhui University of Chinese Medicine, Hefei, Anhui, 230038, China.
authors.forename: Delin
authors.initials: D
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
authors.forename: Liucheng
authors.initials: L
authors.lastname: Li
authors.affiliation: The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, Anhui, 230032, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yao
authors.affiliation: The Second Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D001761:Bleomycin; D002460:Cell Line; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D051379:Mice; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D051267:NF-E2-Related Factor 2; D000071250:Snail Family Transcription Factors; D053773:Transforming Growth Factor beta1; D001761:Bleomycin