As shown hesperidin suppresses TGF-β2-induced proliferation and epithelial-mesenchymal transition of retinal pigment epithelial cells

IF 2.9 4区 生物学 Q3 CELL BIOLOGY
Ayça Küpeli Çınar, Riza Serttas, Abdulkadir Can Çınar, Hande Güçlü, Suat Erdogan
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引用次数: 0

Abstract

This study investigates the potential therapeutic effects and molecular mechanisms of hesperidin treatment on cell migration and epithelial-mesenchymal transition, key stages of proliferative vitreoretinopathy (PVR). Human retinal pigment epithelial cells (ARPE-19) were treated with 10 ng/ml transforming growth factor-beta 2 (TGF-β2) alone or in combination with 1.56 μM hesperidin for 48 h. The impact of treatment on cell migration was evaluated using a wound healing assay. Apoptosis was assessed using DNA staining. mRNA and protein expression were evaluated using real-time PCR and Western blot, respectively. Hesperidin inhibits the proliferation and transformation of the cells by inducing apoptosis and reverses the cell morphology modified by TGF-β2. Hesperidin inhibits cell migration induced by TGF-β2. Upon treatment with hesperidin, the levels of mesenchymal markers upregulated by TGF-β2, such as MMP-1, -2, -9, fibronectin, α-SMA and the transcription factors Snail, Slug and ZEB-1, were downregulated. Conversely, the epithelial marker E-cadherin is upregulated with hesperidin treatment. Additionally, TIMP-1 and TIMP-2 expression levels, which are downregulated, increase with the treatment. These results suggest that hesperidin may inhibit the migration and EMT processes of RPE cells involved in the development of PVR, indicating its potential as a therapeutic agent for treating PVR.

Abstract Image

如图所示,橙皮甙能抑制 TGF-β2 诱导的视网膜色素上皮细胞增殖和上皮-间质转化
本研究探讨了橙皮甙治疗对细胞迁移和上皮-间质转化(增殖性玻璃体视网膜病变(PVR)的关键阶段)的潜在治疗作用和分子机制。用 10 ng/ml 转化生长因子-β2(TGF-β2)单独或与 1.56 μM 橙皮素联合处理人视网膜色素上皮细胞(ARPE-19)48 小时。mRNA 和蛋白质表达分别通过实时 PCR 和 Western 印迹进行评估。橙皮甙通过诱导细胞凋亡抑制细胞的增殖和转化,并逆转 TGF-β2 改变的细胞形态。橙皮甙能抑制 TGF-β2 诱导的细胞迁移。经橙皮甙处理后,TGF-β2 上调的间质标志物,如 MMP-1、-2、-9、纤连蛋白、α-SMA 以及转录因子 Snail、Slug 和 ZEB-1 的水平下调。相反,上皮标志物 E-cadherin 在橙皮素处理后上调。此外,下调的 TIMP-1 和 TIMP-2 表达水平也会随着治疗的进行而增加。这些结果表明,橙皮甙可抑制参与 PVR 发生的 RPE 细胞的迁移和 EMT 过程,表明它有可能成为治疗 PVR 的一种药物。
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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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