The role of lipid peroxidation in epithelial-mesenchymal transition of retinal pigment epithelial cells.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Epithelial-Mesenchymal Transition*/drug effects ; Retinal Pigment Epithelium*/metabolism ; Lipid Peroxidation*; Humans ; Cell Line ; Cell Movement/drug effects ; Tumor Necrosis Factor-alpha/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Transforming Growth Factor beta2/metabolism ; Epithelial Cells/metabolism ; Reactive Oxygen Species/metabolism ; Cell Survival/drug effects ; Zinc Finger E-box-Binding Homeobox 1/metabolism ; Zinc Finger E-box-Binding Homeobox 1/genetics ; Cell Proliferation ; Zonula Occludens-1 Protein/metabolism ; Fibronectins/metabolism

Epithelial-Mesenchymal Transition (EMT) of retinal pigment epithelial (RPE) cells is recognized as pivotal in various retinal diseases. Previous studies have suggested a reciprocal regulation between reactive oxygen species (ROS) and EMT, though the involvement of peroxidized lipids or the effects of reducing them has remained unclear. The present study disclosed that EMT of ARPE-19 cells induced by TGF-β2 and TNF-α involves increased lipid peroxidation, and Ferrostatin-1 (Fer-1), a lipophilic antioxidative agent, successfully inhibited the increase in lipid peroxidation. Fer-1 suppressed the formation of EMT-associated fibrotic deposits, while EMT induction or Fer-1 treatment did not influence the cell viability or proliferation. Functionally, Fer-1 impeded EMT-driven cell migration and reduction in transepithelial electrical resistance. It demonstrated regulatory prowess by downregulating the mesenchymal marker fibronectin, upregulating the epithelial marker ZO-1, and inhibiting the EMT-associated transcriptional factor ZEB1. Additionally, VEGF, a major pathogenic cytokine in various retinal diseases, is also upregulated during EMT, and Fer-1 significantly mitigated the effect. The present study disclosed the involvement of lipid peroxidation in EMT of RPE cells, and suggests the suppression of lipid peroxidation may be a potential therapeutic target in retinal diseases in which EMT is implicated.
(© 2024. The Author(s).)

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19K18872 Japan Society for the Promotion of Science; 21K09758 Japan Society for the Promotion of Science

Keywords: ARPE-19; Epithelial–mesenchymal transition; Ferrostatin-1; Lipid peroxidation; Retinal pigment epithelium

0 (Tumor Necrosis Factor-alpha)
0 (Vascular Endothelial Growth Factor A)
0 (Transforming Growth Factor beta2)
0 (Reactive Oxygen Species)
0 (Zinc Finger E-box-Binding Homeobox 1)
0 (ZEB1 protein, human)
0 (Zonula Occludens-1 Protein)
0 (Fibronectins)

Date Created: 20240717 Date Completed: 20240717 Latest Revision: 20240802

20240802

PMC11255318

10.1038/s41598-024-67587-5

39020017