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Astragaloside IV attenuates high-glucose-Induced peritoneal fibrosis via modulation of the ENKUR/PI3K/Akt signalling pathway

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  • Tianxin Jiang
  • Lijie Zhang
  • Jiahan Liu
  • Xinxin Xu
  • Yuanyuan Shi
  • Zhanzheng Zhao
  • Jing Xiao

Abstract

This study aimed to explore the mechanisms by which Astragaloside IV (AS-IV), a major bioactive component of Astragalus membranaceus, mitigates high-glucose-induced peritoneal fibrosis (PF) in peritoneal dialysis (PD). Using both in vivo (uremic rat model) and in vitro (human peritoneal mesothelial cells) approaches, we observed that AS-IV treatment was associated with a significant attenuation of PF. This effect was mediated through the inhibition of epithelial-mesenchymal transition (EMT) and fibrosis. In vivo, AS-IV reduced extracellular matrix deposition and collagen accumulation, downregulated EMT and fibrosis markers (α-SMA, collagen IV), and restored E-cadherin levels. Notably, these changes correlated with the downregulation of ENKUR, pPI3K, and pAkt. The in vitro results corroborated these findings, showing that AS-IV suppressed EMT without cytotoxic effects. Our data indicate that AS-IV may exert antifibrotic effects via modulation of the ENKUR/PI3K/Akt signaling pathway, suggesting a potential target for the prevention of PF.

Suggested Citation

  • Tianxin Jiang & Lijie Zhang & Jiahan Liu & Xinxin Xu & Yuanyuan Shi & Zhanzheng Zhao & Jing Xiao, 2026. "Astragaloside IV attenuates high-glucose-Induced peritoneal fibrosis via modulation of the ENKUR/PI3K/Akt signalling pathway," PLOS ONE, Public Library of Science, vol. 21(5), pages 1-13, May.
    • Handle: RePEc:plo:pone00:0348762
    DOI: 10.1371/journal.pone.0348762
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