Abstract: TH-PO848

Astragalus Inhibits Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells via Suppressing Wnt/β-Catenin Signaling and Promoting Smad7

Session Information

  • Peritoneal Dialysis - I
    November 02, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Dialysis

  • 608 Peritoneal Dialysis

Authors

  • Shi, Jun, First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
  • Yu, Manshu, First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
  • Gao, Kun, Department of nephrology,the affiliated hospital of Nanjing University of Chinese Medicine, Nanjing, China
  • Zhang, Lu, Department of nephrology,the affiliated hospital of Nanjing University of Chinese Medicine, Nanjing, China
  • Sheng, Meixiao, Department of nephrology,the affiliated hospital of Nanjing University of Chinese Medicine, Nanjing, China
Background

Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a crucial event inducing peritoneal fibrosis (PF), in which Wnt/β-catenin signaling participates. Smads signaling is reported to interact with β-catenin and synergistically regulates EMT. This study was aimed to reveal the effect of Astragalus(a famous Chinese herbal)on Wnt/β-catenin signaling in PMCs with EMT, as well as on the crosstalk between β-catenin and Smads.

Methods

Rats with peritoneal fibrosis and the human HMrSV5 peritoneal mesothelial cell line were used to explore the effects of Astragalus on EMT. EMT markers or signaling pathway-related indicators were detected by Western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation and rt-PCR.

Results

β-Catenin knockdown inhibited EMT of PMCs. Astragalus not only relieved EMT and peritoneal fibrosis in rats but also inhibited β-catenin-mediated EMT in the HMrSV5 cell line, resulting from increased E-cadherin and decreased α-SMA. The nuclear translocation of β-catenin was suppressed by Astragalus as a result of the stabilization of GSK-3β promoting dissociative β-catenin degradation. Smad7, which was associated with β-catenin, was enhanced by Astragalus during EMT. The knockdown of Smad7 induced an increase in β-catenin and EMT.

Conclusion

Astragalus promotes Smad7 expression and effectively inhibits the Wnt/β-catenin signaling pathway during EMT of PMCs, indicating its potential therapeutic effect for PF.

Funding

  • Government Support - Non-U.S.