Dihydroartemisinin up-regulates VE-cadherin expression in human renal glomerular endothelial cells

J Cell Mol Med. 2018 Mar;22(3):2028-2032. doi: 10.1111/jcmm.13448. Epub 2017 Nov 29.

Abstract

The antimalarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we found that DHA increased the expression of the junctional protein vascular endothelial (VE)-cadherin in human renal glomerular endothelial cells. In addition, DHA inhibited TGF-β RI-Smad2/3 signalling and its downstream effectors SNAIL and SLUG, which repress VE-cadherin gene transcription. Correspondingly, DHA decreased the binding of SNAIL and SLUG to the VE-cadherin promoter. Together, our results suggest an effect of DHA in regulating glomerular permeability by elevation of VE-cadherin expression.

Keywords: TGF-β signalling; VE-cadherin; dihydroartemisinin; glomerular endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Antimalarials / pharmacology
  • Artemisinins / pharmacology*
  • Cadherins / agonists
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Line
  • Drug Repositioning
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Signal Transduction
  • Smad2 Protein / antagonists & inhibitors
  • Smad2 Protein / genetics*
  • Smad2 Protein / metabolism
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism
  • Snail Family Transcription Factors / genetics
  • Snail Family Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / antagonists & inhibitors
  • Transforming Growth Factor beta1 / genetics*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antigens, CD
  • Antimalarials
  • Artemisinins
  • Cadherins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SNAI1 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Snail Family Transcription Factors
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • cadherin 5
  • artenimol