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Published on: October 27, 2020
Astragalus Inhibits Epithelial-to-Mesenchymal Transition of Peritoneal Mesothelial Cells by Down-Regulating β-Catenin
Background/Aims:
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. This study was aimed to reveal the effect of Astragalus on β-catenin in EMT of PMCs.
Methods:
To obtain the role of β-catenin in EMT, gene transfer into HMrSV5 cell line and rats has been achieved. After Astragalus treatment, EMT markers and signaling pathway-related indicators were detected by western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation and real time-PCR.
Results:
β-catenin knockdown suppressed EMT of HMrSV5 cells. Astragalus alleviated EMT of PMCs characterized by increased E-cadherin and decreased α-SMA and Vimentin. In rat model of peritoneal dialysis (PD), Astragalus attenuated peritoneal thickening and fibrosis. Astragalus down-regulated β-catenin by stabilizing the Glycogen synthase kinase-3β (GSK-3β)/β-catenin complex and further inhibited the nuclear translocation of β-catenin. Meanwhile, Astragalus down-regulated β-catenin by enhancing Smad7 expression. Silencing Smad7 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.
Insights
Astragalus inhibits epithelial-to-mesenchymal transition (EMT) in peritoneal mesothelial cells (PMCs) by reducing β-catenin. This finding offers a potential therapeutic strategy for preventing peritoneal fibrosis (PF).
Area of Science:
- Cell Biology
- Molecular Biology
- Pharmacology
Background:
- Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is key to peritoneal fibrosis (PF).
- Wnt/β-catenin signaling and Smad signaling pathways are implicated in EMT and interact with β-catenin.
- Understanding Astragalus's effect on β-catenin in PMC EMT is crucial for developing PF treatments.
Purpose of the Study:
- To investigate the role of β-catenin in EMT of PMCs.
- To determine the effect of Astragalus on β-catenin and EMT in PMCs.
- To explore the therapeutic potential of Astragalus in preventing peritoneal fibrosis.
Main Methods:
- Gene transfer in HMrSV5 cell line and rats to study β-catenin's role in EMT.
- Astragalus treatment followed by analysis of EMT markers and signaling pathways.
- Techniques included western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation, and real-time PCR.
Main Results:
- β-catenin knockdown inhibited EMT in HMrSV5 cells.
- Astragalus treatment reduced EMT markers (increased E-cadherin, decreased α-SMA and Vimentin) in PMCs.
- Astragalus attenuated peritoneal thickening and fibrosis in a rat model, down-regulating β-catenin via GSK-3β stabilization and enhancing Smad7 expression.
Conclusions:
- Astragalus inhibits PMC EMT by down-regulating β-catenin.
- Modulating peritoneal β-catenin presents a novel approach for preventing peritoneal fibrosis.
- Astragalus demonstrates therapeutic potential for peritoneal fibrosis treatment.
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