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Toxins 2017, 9(4), 138; doi:10.3390/toxins9040138

Suppression of Hepatic Epithelial-to-Mesenchymal Transition by Melittin via Blocking of TGFβ/Smad and MAPK-JNK Signaling Pathways

1
College of Pharmacy, Keimyung University, Dalgubeoldaero, Dalseo-Gu, Daegu 42601, Korea
2
Department of Pathology, Daegu Catholic University Medical Center, Duryugongwon-ro, Nam-gu, Daegu 42472, Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Michel Dugon
Received: 31 January 2017 / Revised: 7 April 2017 / Accepted: 10 April 2017 / Published: 13 April 2017
(This article belongs to the Section Animal Venoms)
View Full-Text   |   Download PDF [4495 KB, uploaded 13 April 2017]   |  

Abstract

Transforming growth factor (TGF)-β1 plays a crucial role in the epithelial-to-mesenchymal transition (EMT) in hepatocytes and hepatic stellate cells (HSC), which contributes to the pathogenesis of liver fibrosis. Melittin (MEL) is a major component of bee venom and is effective in rheumatoid arthritis, pain relief, cancer cell proliferation, fibrosis and immune modulating activity. In this study, we found that MEL inhibits hepatic EMT in vitro and in vivo, regulating the TGFβ/Smad and TGFβ/nonSmad signaling pathways. MEL significantly inhibited TGF-β1-induced expression of EMT markers (E-cadherin reduction and vimentin induction) in vitro. These results were confirmed in CCl4-induced liver in vivo. Treatment with MEL almost completely blocked the phosphorylation of Smad2/3, translocation of Smad4 and phosphorylation of JNK in vitro and in vivo. Taken together, these results suggest that MEL suppresses EMT by inhibiting the TGFβ/Smad and TGFβ/nonSmad-c-Jun N-terminal kinase (JNK)/Mitogen-activated protein kinase (MAPK) signaling pathways. These results indicated that MEL possesses potent anti-fibrotic and anti-EMT properties, which may be responsible for its effects on liver diseases. View Full-Text
Keywords: melittin; epithelial-to-mesenchymal transition; transforming growth factor; liver diseases melittin; epithelial-to-mesenchymal transition; transforming growth factor; liver diseases
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Park, J.-H.; Park, B.; Park, K.-K. Suppression of Hepatic Epithelial-to-Mesenchymal Transition by Melittin via Blocking of TGFβ/Smad and MAPK-JNK Signaling Pathways. Toxins 2017, 9, 138.

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