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Sulforaphane protects against ethanol-induced apoptosis in neural crest cells through restoring epithelial-mesenchymal transition by epigenetically modulating the expression of Snail1.

ABSTRACT: Ethanol-induced apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is implicated in the Fetal Alcohol Spectrum Disorders (FASD). Studies have demonstrated that sulforaphane (SFN) can prevent ethanol-induced apoptosis in NCCs. The objective of this study is to investigate whether ethanol exposure can induce apoptosis in NCCs by inhibiting epithelial-mesenchymal transition (EMT) and whether SFN can prevent ethanol-induced apoptosis by epigenetically modulating the expression of Snail1, a key transcriptional factor that promotes EMT. We found that ethanol exposure resulted in a significant increase in apoptosis in NCCs. Co-treatment with SFN significantly reduced ethanol-induced apoptosis. Treatment with SFN also dramatically diminished ethanol-induced changes in the expression of E-cadherin and vimentin, and restored EMT in ethanol-exposed NCCs. In addition, ethanol exposure reduced the levels of trimethylation of histone H3 lysine 4 (H3K4me3) at the promoters of Snail1. SFN treatment diminished the ethanol-induced reduction of H3K4me3 at the promoter regions of the Snail1 gene, restored the expression of Snail1 and down-regulated Snail1 target gene E-cadherin. Knockdown of Snail1 significantly reduced the protective effects of SFN on ethanol-induced apoptosis. These results demonstrate that SFN can protect against ethanol-induced apoptosis by preventing ethanol-induced reduction in the levels of H3K4me3 at the promoters of Snail1, restoring the expression of Snail1 and EMT in ethanol-exposed NCCs.

SUBMITTER: Li Y

PROVIDER: S-EPMC6708741 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Sulforaphane protects against ethanol-induced apoptosis in neural crest cells through restoring epithelial-mesenchymal transition by epigenetically modulating the expression of Snail1.

Li Yihong Y Yuan Fuqiang F Wu Ting T Lu Lanhai L Liu Jie J Feng Wenke W Chen Shao-Yu SY

Biochimica et biophysica acta. Molecular basis of disease 20190708 10

Ethanol-induced apoptosis in neural crest cells (NCCs), a multipotent progenitor cell population, is implicated in the Fetal Alcohol Spectrum Disorders (FASD). Studies have demonstrated that sulforaphane (SFN) can prevent ethanol-induced apoptosis in NCCs. The objective of this study is to investigate whether ethanol exposure can induce apoptosis in NCCs by inhibiting epithelial-mesenchymal transition (EMT) and whether SFN can prevent ethanol-induced apoptosis by epigenetically modulating the ex ...[more]

PMID: 31295528

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Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective treatment. The epithelial-mesenchymal transition (EMT) is a critical stage during the development of fibrosis. To assess the effect of sulforaphane (SFN) on the EMT and fibrosis using an in vitro transforming growth factor (TGF)-?1-induced model and an in vivo bleomycin (BLM)-induced model.In vitro studies, cell viability, and cytotoxicity were measured using a Cell Counting Kit-8. The functional TGF-?1-induced EMT and fibrosis were assessed using western blotting and a quantitative real-time polymerase chain reaction. The lungs were analyzed histopathologically in vivo using hematoxylin and eosin and Masson's trichrome staining. The BLM-induced fibrosis was characterized by western blotting and immunohistochemical analyses for fibronectin, TGF-?1, E-cadherin (E-cad), and ?-smooth muscle actin (SMA) in lung tissues.SFN reversed mesenchymal-like changes induced by TGF-?1 and restored cells to their epithelial-like morphology. The results confirmed that the expression of the epithelial marker, E-cadherin, increased after SFN treatment, while expression of the mesenchymal markers, N-cadherin, vimentin, and ?-SMA decreased in A549 cells after SFN treatment. In addition, SFN inhibited TGF-?1-induced mRNA expression of the EMT-related transcription factors, Slug, Snail, and Twist. The SFN treatment attenuated TGF-?1-induced expression of fibrosis-related proteins, such as fibronection, collagen I, collagen IV, and ?-SMA in MRC-5 cells. Furthermore, SFN reduced the TGF-?1-induced phosphorylation of SMAD2/3 protein in A549 cells and MRC-5 cells. BLM induced fibrosis in mouse lungs that was also attenuated by SFN treatment, and SFN treatment decreased BLM-induced fibronectin expression, TGF-?1 expression, and the levels of collagen I in the lungs of mice.SFN showed a significant anti-fibrotic effect in TGF-?-treated cell lines and BLM-induced fibrosis in mice. These findings showed that SFN has anti-fibrotic activity that may be considered in the treatment of IPF.

Dataset Information

Sulforaphane protects against ethanol-induced apoptosis in neural crest cells through restoring epithelial-mesenchymal transition by epigenetically modulating the expression of Snail1.

Publications

Sulforaphane protects against ethanol-induced apoptosis in neural crest cells through restoring epithelial-mesenchymal transition by epigenetically modulating the expression of Snail1.

Similar Datasets

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