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Inhibition of the tubular epithelial-to-mesenchymal transition in vivo and in vitro by the Uremic Clearance Granule (尿毒清颗粒)

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Abstract

Objective

To investigate the effect of the Uremic Clearance Granule (UCG, 尿毒清颗粒), a Chinese patent medicine, on tubular epithelial-to-mesenchymal transition (EMT) in a unilateral ureteral obstruction (UUO) model in vivo and transforming growth factor (TGF)-β1 induced EMT of HK-2 cells in vitro.

Methods

In vivo study, 50 Sprague Dawley rats were divided into three groups: a sham operation group (n=10), a UUO group (n=20), and a UUO with UCG treatment group (n=20). The UCG was given at a dose of 4.5 g/kg body weight per day by gavage after surgery. In vitro study, HK-2 cells were cultured in 10% fetal bovine serum (FBS), 10% healthy rat serum, 10% FBS and TGF-β1 (10 ng/mL), 10% healthy rat serum and TGF-β1, or 10% rat serum containing the uremic clearance granule and TGF-β1. The expression of the epithelial marker E-cadherin and the mesenchymal markers vimentin and α-smooth muscle actin (α-SMA) in kidney tissues and HK-2 cells were investigated by Western blot analysis and immunofluorescence staining.

Results

The rats of the UUO group showed obvious tubulointerstitial fibrosis, compared with the sham operation group rats. Tubulointerstitial fibrosis score was reduced by 17.5%±1.1% at day 7 and by 20.0%±1.2% at day 14 in the UCG-treated group, compared with the UUO group. The UCG could maintained expression of E-cadherin and suppressed expression of vimentin and α-SMA in kidney tissues of UUO rats at days 7 and 14, as determined by Western blot analysis and immunofluorescence staining. Rat serum containing the UCG partially inhibited TGF-β1-induced fibroblast phenotype of HK-2 cells and maintained the epithelial morphology of HK-2 cells in vitro. This occurred partially through a reduction of vimentin expression and an increase of E-cadherin expression.

Conclusion

These results suggest that the UCG prevents tubular EMT and may be a promising agent for treating tubulointerstitial fibrosis.

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Authors and Affiliations

  1. Institute of Nephrology, State Key Laboratory of Kidney Disease (2011DAV00088), Chinese PLA General Hospital, Beijing, 100853, China

    Zhao-yu Lu  (卢钊宇), Shu-wen Liu  (刘述文), Yuan-sheng Xie  (谢院生), Shao-yuan Cui  (崔少远), Wen-jia Geng  (耿文佳), Xiao Hu  (呼 啸), Jia-yao Ji  (季佳瑶) & Xiang-mei Chen  (陈香美)

  2. Department of Nephrology, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

    Zhao-yu Lu  (卢钊宇), Xu-sheng Liu  (刘旭生) & Wen-jia Geng  (耿文佳)

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  1. Zhao-yu Lu  (卢钊宇)
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  2. Shu-wen Liu  (刘述文)
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  3. Yuan-sheng Xie  (谢院生)
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  4. Shao-yuan Cui  (崔少远)
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  5. Xu-sheng Liu  (刘旭生)
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  6. Wen-jia Geng  (耿文佳)
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  7. Xiao Hu  (呼 啸)
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  8. Jia-yao Ji  (季佳瑶)
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  9. Xiang-mei Chen  (陈香美)
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Corresponding authors

Correspondence to Yuan-sheng Xie  (谢院生) or Xiang-mei Chen  (陈香美).

Additional information

Supported by the National Basic Research Program of China (No. 2011CB944004), the Program of the National Natural Science Foundation of China (No. 30971377) and the Science and Technology Project of Beijing, China (No. D09050704310904)

These authors contributed equally to this work

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Lu, Zy., Liu, Sw., Xie, Ys. et al. Inhibition of the tubular epithelial-to-mesenchymal transition in vivo and in vitro by the Uremic Clearance Granule (尿毒清颗粒). Chin. J. Integr. Med. 19, 918–926 (2013). https://doi.org/10.1007/s11655-013-1654-9

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  • DOI: https://doi.org/10.1007/s11655-013-1654-9

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