Bone morphogenetic protein-7 regulates Snail signaling in carbon tetrachloride-induced fibrosis in the rat liver

Bi,Wan-Rong; Jin,Cai-Xia; Xu,Guo-Tong; Yang,Chang-Qing

doi:10.3892/etm.2012.720

December 2012 Volume 4 Issue 6

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December 2012 Volume 4 Issue 6

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Article

Bone morphogenetic protein-7 regulates Snail signaling in carbon tetrachloride-induced fibrosis in the rat liver

Authors:
- Wan-Rong Bi
- Cai-Xia Jin
- Guo-Tong Xu
- Chang-Qing Yang
View Affiliations / Copyright

Affiliations: Department of Gastroenterology and Digestive Disease Institute, Tongji Hospital, Tongi University School of Medicine, Shanghai 200090, P.R. China, Stem Cell Laboratory, Shanghai 200092, P.R. China, Department of Gastroenterology and Digestive Disease Institute, Tongji Hospital, Tongi University School of Medicine, Shanghai 200065, P.R. China
Pages: 1022-1026
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Published online on: September 24, 2012

https://doi.org/10.3892/etm.2012.720
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Abstract

The aim of this study was to explore the molecular mechanism of the bone morphogenetic protein-7 (BMP-7) downregulation of Snail-mediated E-cadherin repression and mesenchymal-epithelial transition (MET) induction, since little is presently known about this issue. In this study, our aim was to elucidate the underlying mechanism by which cells acquire liver fibrosis characteristics after epithelial-mesenchymal transition (EMT). Cell cultures were exposed to Snail alone or in the presence of BMP-7; control cultures were exposed to medium only. The expression of the mRNA encoding α-smooth muscle actin (α-SMA), Snail and E-cadherin in rat liver epithelial cells was determined by real-time quantitative PCR (RT-PCR) and the main results were confirmed by ELISA. Cell differentiation was determined by analysis of the expression of α-SMA, Snail and E-cadherin by western blotting and co-immunoprecipitation. We demonstrated Snail-induced upregulation of mRNAs encoding α-SMA and downregulation of mRNAs encoding E-cadherin in rat liver epithelial cells when compared with unstimulated cells, and confirmed these results at the protein level. BMP-7 downregulated Snail-induced α-SMA and upregulated E-cadherin release compared with untreated and Snail-treated cells. In summary, we demonstrated that BMP-7 induces MET through decreased downregulation of Snail. In addition, Snail1 directly regulates Nanog promoter activity. Notch signaling is also involved in this process.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Bone morphogenetic protein-7 regulates Snail signaling in carbon tetrachloride-induced fibrosis in the rat liver

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Abstract

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