Artesunate inhibits the development of PVR by suppressing the TGF-β/Smad signaling pathway

Exp Eye Res. 2021 Dec:213:108859. doi: 10.1016/j.exer.2021.108859. Epub 2021 Nov 23.

Abstract

Proliferative vitreoretinopathy (PVR) is the main cause of retinal detachment surgery failure. The epithelial-mesenchymal transition (EMT) induced by transforming growth factor (TGF-β2) plays an important role in the development of PVR. Artesunate has been widely studied as a treatment for ophthalmic diseases because of its antioxidant, anti-inflammatory, antiapoptotic and antiproliferative properties. The purpose of this study was to investigate the effects of artesunate on the TGF-β2-induced EMT in ARPE-19 cells and PVR development. We found that artesunate inhibited the proliferation and contraction of ARPE-19 cells after the EMT and the autocrine effects of TGF-β2 on ARPE-19 cells. Additionally, the levels of Smad3 and p-Smad3 were increased in clinical samples, and artesunate decreased the levels of Smad3 and p-Smad3 in ARPE-19 cells treated with TGF-β2. Artesunate also inhibited the occurrence and development of PVR in vivo. In summary, artesunate inhibits the occurrence and development of PVR by inhibiting the EMT in ARPE-19 cells.

Keywords: Artesunate; Epithelial-mesenchymal transition; Growth factor; Proliferative vitreoretinopathy; Transforming.

MeSH terms

  • Animals
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use*
  • Artesunate / pharmacology
  • Artesunate / therapeutic use*
  • Blotting, Western
  • Cell Cycle / physiology
  • Cell Line
  • Cell Movement / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial-Mesenchymal Transition / drug effects*
  • Flow Cytometry
  • Humans
  • Intravitreal Injections
  • Rabbits
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Signal Transduction / drug effects
  • Smad3 Protein / antagonists & inhibitors*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta2 / antagonists & inhibitors*
  • Transforming Growth Factor beta2 / metabolism
  • Vitreoretinopathy, Proliferative / drug therapy*
  • Vitreoretinopathy, Proliferative / metabolism

Substances

  • Antimalarials
  • SMAD3 protein, human
  • Smad3 Protein
  • TGFB2 protein, human
  • Transforming Growth Factor beta2
  • Artesunate