Particulate matter 2.5 exposure induces epithelial-mesenchymal transition via PI3K/AKT/mTOR pathway in human retinal pigment epithelial ARPE-19 cells

Biochem Biophys Res Commun. 2022 Aug 30;617(Pt 2):11-17. doi: 10.1016/j.bbrc.2022.05.072. Epub 2022 Jun 3.

Abstract

Exposure to particulate matter 2.5 (PM2.5) has been linked to ocular surface diseases, yet knowledge of the molecular mechanism impacted on retina pathogenesis is limited. Therefore, the purpose of this study was to explore the effects and involved factors of PM2.5 exposure in human retinal pigment epithelial APRE-19 cells. Our data revealed a decreased cell viability and an increased migratory ability in APRE-19 cells after PM2.5 stimulation. The MMP-2 and MMP-9 protein levels were markedly increased while the MMPs regulators TIMP-1 and TIMP-2 were significantly reduced in PM2.5-exposed APRE-19 cells. PM2.5 also increased pro-MMP-2 expression in the cell culture supernatants. Additionally, PM2.5 promoted the EMT markers through the activation of PI3K/AKT/mTOR pathway. Moreover, the ICAM-1 production was also remarkably increased by PM2.5 but reduced by PI3K/AKT inhibitor LY294002 in APRE-19 cells. Taken together, these results suggest that PM2.5 promotes EMT in a PI3K/AKT/mTOR-dependent manner in the retinal pigment epithelium.

Keywords: Epithelial-mesenchymal transition; Ocular surface diseases; PI3K/AKT/mTOR signaling; PM2.5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition
  • Humans
  • Particulate Matter* / toxicity
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Retinal Pigments / metabolism
  • Retinal Pigments / pharmacology
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Particulate Matter
  • Phosphoinositide-3 Kinase Inhibitors
  • Retinal Pigments
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases