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

Autor: Suat Erdogan, Riza Serttas, Ayça Küpeli Çınar, S Altan Ozal
Rok vydání: 2021
Předmět:
Proliferative vitreoretinopathy
Epithelial-Mesenchymal Transition
Eupatilin
Retinal Pigment Epithelium
Toxicology
Cell Line
Cell Physiological Phenomena
Transforming Growth Factor beta2
030207 dermatology & venereal diseases
03 medical and health sciences
chemistry.chemical_compound
Pigment
0302 clinical medicine
Antigens
CD
Occludin
medicine
Humans
Vimentin
Epithelial–mesenchymal transition
Flavonoids
Transition (genetics)
Chemistry
Twist-Related Protein 1
Vitreoretinopathy
Proliferative
Nuclear Proteins
Zinc Finger E-box-Binding Homeobox 1
Epithelial Cells
Retinal
General Medicine
Adhesion
Cadherins
medicine.disease
Matrix Metalloproteinases
eye diseases
Fibronectins
Cell biology
visual_art
030221 ophthalmology & optometry
visual_art.visual_art_medium
Snail Family Transcription Factors
sense organs
Transforming growth factor
medicine.drug
Zdroj: Cutaneous and Ocular Toxicology. 40:103-114
ISSN: 1556-9535
1556-9527
Popis: 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.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.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.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.
Databáze: OpenAIRE
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