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Original Articles

Eupatilin attenuates TGF-β2-induced proliferation and epithelial-mesenchymal transition of retinal pigment epithelial cells

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 103-114 | Received 12 Jan 2021, Accepted 09 Mar 2021, Published online: 08 Apr 2021
 

Abstract

Purpose

The main characteristic of proliferative vitreoretinopathy (PVR) is migration, adhesion, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE). Eupatilin is a naturally occurring flavone that has the potential to inhibit cell proliferation and EMT. However, its efficacy on the PVR model induced by transforming growth factor-2 (TGF-β2) is unknown. In this study, the potential effect of eupatilin on proliferation and EMT in the treatment of RPE was investigated.

Methods

Serum starved human RPE cells (ARPE-19) were treated with 10 ng/ml TGF-β2 alone or co-treated with 25 μM eupatilin for 48 h. Quantitative real-time PCR and Western blot analysis were used to assess targets at the mRNA and protein expression level, respectively. Apoptosis and cell cycle progression was assessed by image-based cytometry. The effect of treatment on cell migration was evaluated by wound healing assay.

Results

Eupatilin inhibited TGF-β2-induced RPE cell proliferation via regulating the cell cycle and inducing apoptosis. TGF-β2 upregulated mRNA expression of mesenchymal markers fibronectin and vimentin was significantly downregulated by the treatment, while the epithelial markers E-cadherin and occludin expression was upregulated. The therapy significantly suppressed TGF-β2 encouraged cell migration through downregulating the expression of transcription factors Twist, Snail, and ZEB1 induced by TGF-β2. Furthermore, eupatilin significantly inhibited the expression of MMP-1, -7, and -9, and suppressed NF-κB signalling.

Conclusion

These results suggest that eupatilin could inhibit the proliferation and transformation into fibroblast-like cells of RPE cells; thus the agent may be a potential therapeutic value in treating PVR.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by the Trakya University Scientific Research Projects Foundation [TUBAP 2019–224].

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