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BMC Pharmacol Toxicol. 2018 Apr 2;19(1):13. doi: 10.1186/s40360-018-0204-7.

Sulforaphane attenuates pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition.

Author information

1
Department of Internal Medicine, Gachon University Gil Medical Center, 21 Namdong-daero 774, Namdong-gu, Incheon, 21565, Republic of Korea.
2
Department of Biological Science, College of Bio-nano Technology, Gachon University, Seongnam-daero 1342, Seongnam, South Korea.
3
Department of Internal Medicine, Gachon University Gil Medical Center, 21 Namdong-daero 774, Namdong-gu, Incheon, 21565, Republic of Korea. jsw@gilhospital.com.

Abstract

BACKGROUND:

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)-β1-induced model and an in vivo bleomycin (BLM)-induced model.

METHODS:

In vitro studies, cell viability, and cytotoxicity were measured using a Cell Counting Kit-8. The functional TGF-β1-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-β1, E-cadherin (E-cad), and α-smooth muscle actin (SMA) in lung tissues.

RESULTS:

SFN reversed mesenchymal-like changes induced by TGF-β1 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 α-SMA decreased in A549 cells after SFN treatment. In addition, SFN inhibited TGF-β1-induced mRNA expression of the EMT-related transcription factors, Slug, Snail, and Twist. The SFN treatment attenuated TGF-β1-induced expression of fibrosis-related proteins, such as fibronection, collagen I, collagen IV, and α-SMA in MRC-5 cells. Furthermore, SFN reduced the TGF-β1-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-β1 expression, and the levels of collagen I in the lungs of mice.

CONCLUSIONS:

SFN showed a significant anti-fibrotic effect in TGF-β-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.

KEYWORDS:

Bleomycin; Epithelial-mesenchymal transition; Idiopathic pulmonary fibrosis; Sulforaphane

PMID:
29609658
PMCID:
PMC5879815
DOI:
10.1186/s40360-018-0204-7
[Indexed for MEDLINE]
Free PMC Article

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