Abstract: SA-PO935
Astragalus Inhibits Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells by Down-regulating β-Catenin
Session Information
- Dialysis: Peritoneal Dialysis - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Authors
- Yu, Manshu, Nanjing University of Chinese Medicine, Nanjing, China
- Shi, Jun, Nanjing University of Chinese Medicine, Nanjing, China
- Sheng, Meixiao, Jiangsu Province Hosiptal of Chinese Medicine, Nanjing, JIANGSU , China
Background
The epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a crucial event in the induction of peritoneal fibrosis (PF), in which canonical Wnt/β-catenin signaling participates. Smads signaling is reported to interact with β-catenin and synergistically regulates EMT. Astragalus is the traditional Chinese herbal which has an effect to restrain the ROS, anti-inflammatory, anti-fibrosis, etc. This study was aimed to reveal the effect of Astragalus on β-catenin in EMT of PMCs.
Methods
The HMrSV5 cell line and gene transfection rats were treated with Astragalus. EMT markers or signaling pathway-related indicators were detected by western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation and real-time PCR.
Results
HMrSV5 EMT model was established by TGF-β1, and the peritoneal fibrosis rat model was established by 4.25% glucose peritoneal dialysis solution. Astragalus inhibited EMT of PMCs including increased E-cadherin and decreased α-SMA and Vimentin, as well as attenuated peritoneal thickening and fibrosis in rats. During the process of PMCs EMT, Astragalus could inhibit β-catenin expression. Astragalus down-regulated β-catenin by stabilizing the GSK-3β/β-catenin complex and further inhibited the nuclear translocation of β-catenin. Meanwhile, Akt is the upstream protein of GSK-3β/β-catenin, which could regulate the degradation of β-catenin. On the other hand, Astragalus down-regulated β-catenin by enhancing Smad7 expression. Silencing Smad7 in HMrSV5 and rats antagonized the EMT-inhibitory effect of Astragalus.
Conclusion
Astragalus inhibits EMT of PMCs by down-regulating β-catenin. The modulation of β-catenin in peritoneum can be a novel tool to prevent PF.
Funding
- Government Support - Non-U.S.