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Open Access Research article

Salvianolic acid B prevents epithelial-to-mesenchymal transition through the TGF-β1 signal transduction pathway in vivo and in vitro

Qing-Lan Wang12, Yan-Yan Tao12, Ji-Li Yuan1, Li Shen1 and Cheng-Hai Liu123*

Author affiliations

1 Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 528 Zhangheng Road, Shanghai, China

2 Key Laboratory of Liver and Kidney Diseases (Shanghai University of Traditional Chinese Medicine), Ministry of Education, 528 Zhangheng Road, Shanghai, China

3 E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, 1200 Cailun Road, Shanghai, China

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Citation and License

BMC Cell Biology 2010, 11:31  doi:10.1186/1471-2121-11-31

Published: 5 May 2010

Abstract

Background

Salvianolic Acid B (Sal B) is a water-soluble component from Danshen (a traditional Chinese herb widely used for chronic renal diseases) with anti-oxidative and cell protective properties. Sal B also has potential protective effects on renal diseases. Tubular epithelial cells can undergo epithelial-to-mesenchymal transition (EMT), which plays an important role in the pathogenesis of renal interstitial fibrosis (RIF) and is mainly regulated by TGF-β1/Smads pathway. The aims of the study are to investigate the effect of Sal B on tubular EMT in vivo and in vitro, and to elucidate its underlying mechanism against EMT related to TGF-β1/Smads pathway.

Results

For in vivo experiments, RIF was induced in rats by oral administration of HgCl2 and prophylaxised with Sal B and vitamin E. The protein expression of E-cadherin was down-regulated, while the expression of α-SMA, TGF-β1, TβR-I, p-Smad2/3 and the activity of matrix metalloproteinase-2 (MMP-2) were up-regulated in kidneys of model rats when compared with those of normal rats. In contrast, Sal B and vitamin E significantly attenuated the expression of α-SMA, TGF-β1, TβR-I, p-Smad2/3, and MMP-2 activity, but increased E-cadherin expression. For in vitro experiments, HK-2 cells were incubated with TGF-β1 to induce EMT, and the cells were co-cultured with 1 and 10 μM Sal B or SB-431542 (a specific inhibitor of TβR-I kinase). TGF-β1 induced a typical EMT in HK-2 cells, while it was blocked by Sal B and SB-431542, as evidenced by blocking morphologic transformation, restoring E-cadherin and CK-18 expression, inhibiting α-SMA expression and F-actin reorganization, and down-regulating MMP-2/9 activities in TGF-β1 mediated HK-2 cells. Furthermore, Sal B and SB-431542 profoundly down-regulated the expressions of TβR-I and p-Smad2/3 but prevented the decreased expression of Smad7 in TGF-β1 stimulated HK-2 cells.

Conclusions

Sal B can prevent tubular EMT in the fibrotic kidney induced by HgCl2 as well as HK-2 cells triggered by TGF-β1, the mechanism of Sal B is closely related to the regulation of TGF-β1/Smads pathway, manifested as the inhibition of TGF-β1 expression, suppression of TβR-I expression and function, down-regulation of Smad2/3 phosphorylation, and restoration of the down-regulation of Smad7, as well as inhibition of MMP-2 activity.