Quercetin inhibits transforming growth factor β1-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells via the Smad pathway

Drug Des Devel Ther. 2018 Dec 6:12:4149-4161. doi: 10.2147/DDDT.S185618. eCollection 2018.

Abstract

Purpose: The purpose of this study was to evaluate the effect and mechanism of quercetin on TGF-β1-induced retinal pigment epithelial (RPE) cell proliferation, migration, and extracellular matrix secretion.

Materials and methods: Cell counting kit-8, transwell, wound-healing assays, and ELISA were used to assess viability, migration, and collagen I secretion, respectively. Western blot analysis and qPCR were employed to detect mRNA and protein expression levels, respectively.

Results: Quercetin suppressed TGF-β1-induced cell proliferation, migration, and collagen I secretion. The results also showed that mRNA and protein expression of epithelial-mesenchymal transition (EMT)-related markers such as alpha-smooth muscle actin and N-cadherin was downregulated by quercetin in TGF-β1-treated RPE cells; conversely, quercetin upregulated the expression of E-cadherin and tight junction protein 1 (ZO-1). In addition, quercetin could inhibit mRNA and protein expression of matrix metalloproteinases. Quercetin may reverse the progression of EMT via the Smad2/3 pathway.

Conclusion: Our results demonstrate the protective effects of quercetin on RPE cell EMT, revealing a potential therapeutic agent for proliferative vitreoretinopathy treatment.

Keywords: epithelial-mesenchymal transition; proliferative vitreoretinopathy; quercetin; transforming growth factor-β1.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Collagen Type I / metabolism
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Phosphorylation
  • Quercetin / pharmacology*
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology
  • Signal Transduction / drug effects
  • Smad Proteins / metabolism*
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Smad4 Protein / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • ACTA2 protein, human
  • Actins
  • Antigens, CD
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • Collagen Type I
  • SMAD2 protein, human
  • SMAD3 protein, human
  • SMAD4 protein, human
  • Smad Proteins
  • Smad2 Protein
  • Smad3 Protein
  • Smad4 Protein
  • TJP1 protein, human
  • Transforming Growth Factor beta1
  • Zonula Occludens-1 Protein
  • Quercetin
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9