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Cryptotanshinone hinders renal fibrosis and epithelial transdifferentiation in obstructive nephropathy by inhibiting

Wei Wang1,2, Pang-Hu Zhou3, Wei Hu4

  • 1Department of Urology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology, Anhui Medical University, Hefei, Anhui, 232200, China.

Oncotarget
|June 22, 2018
PubMed

Insights

This study shows that Compound X (CTS) reduces kidney fibrosis and epithelial-to-mesenchymal transition (EMT) in mice and cell models. CTS works by inhibiting the TGF-β1/Smad3/integrin β1 pathway, offering a potential therapeutic strategy for kidney diseases.

Area of Science:

  • Nephrology
  • Cell Biology
  • Pharmacology

Background:

  • Cardiac fibrosis can be alleviated by Compound X (CTS).
  • The effects of CTS on kidney fibrosis and epithelial-to-mesenchymal transition (EMT) remain largely unknown.
  • Kidney fibrosis is a significant contributor to chronic kidney disease progression.

Purpose of the Study:

  • To investigate the potential of CTS in attenuating tubulointerstitial fibrosis and EMT.
  • To explore the underlying molecular mechanisms by which CTS exerts its effects.
  • To determine if CTS impacts the TGF-β1/Smad3/integrin β1 signaling pathway.

Main Methods:

  • Established an in vivo unilateral ureter obstruction (UUO) mouse model.
  • Developed an in vitro TGF-β1 stimulated renal tubular epithelial cell model.
  • Administered CTS (50 mg kg-1 day-1) to UUO mice and treated cell models.

Main Results:

  • CTS significantly decreased kidney injury, fibronectin, and collagen-1 accumulation in UUO mice.
  • CTS reduced alpha-smooth muscle actin (α-SMA) expression while preserving E-cadherin in obstructed kidneys.
  • In vitro, CTS suppressed fibronectin, collagen-1, and α-SMA, and preserved E-cadherin, while inhibiting Smad3 activation and nuclear translocation of Smad2/3/4.

Conclusions:

  • CTS ameliorates kidney fibrosis and EMT.
  • CTS acts, at least partly, by inhibiting the TGF-β1/Smad3/integrin β1 signaling pathway.
  • CTS demonstrates potential as a therapeutic agent for kidney fibrosis.
Keywords:
Smad3cryptotanshinoneepithelial-mesenchymal transitionintegrin β1kidney fibrosis

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