关键词: BMP‐6 p38 proliferative vitreoretinopathy retinal pigment epithelium tricetin

Mesh : Humans Retinal Pigment Epithelium / drug effects metabolism cytology Cell Movement / drug effects Bone Morphogenetic Protein 6 / metabolism Cell Line p38 Mitogen-Activated Protein Kinases / metabolism MAP Kinase Signaling System / drug effects Signal Transduction / drug effects

来  源:   DOI:10.1002/tox.24294

Abstract:
Proliferative vitreoretinopathy (PVR) is a visual-threatening disease, which cause from the migration of retinal pigment epithelium (RPE). Tricetin, a family of flavonoids, can inhibit the metastasis of several cancers. Herein, we aim to evaluate the possible effect of tricetin on inhibiting ARPE-19 cells migration. The Boyden chamber assay, wound healing assay, RNA sequencing, and Western blot analysis were applied in our experiment. The results revealed that tricetin inhibited the cell migration abilities of ARPE-19 cells. Moreover, using RNA sequencing technology, we revealed that tricetin repressed bone morphogenetic protein-6 (BMP-6) gene expressions in ARPE-19 cells. Overexpression of BMP-6 resulted in significant restoration of cell migration capabilities of tricetin-treated ARPE-19 cells. Furthermore, tricetin suppressed the phosphorylation of the p38 signaling pathway. Moreover, blocking the p38 pathway also inhibits BMP-6 expression and migration in the ARPE-19 cells. In conclusion, this study revealed that tricetin inhibits the ARPE-19 cell migration mainly via the suppression of BMP-6 expression and p38 signaling pathway.
摘要:
增生性玻璃体视网膜病变(PVR)是一种威胁视觉的疾病,导致视网膜色素上皮(RPE)迁移。Tricetin,一个类黄酮家族,可以抑制几种癌症的转移。在这里,我们的目的是评估三酸对ARPE-19细胞迁移的抑制作用。Boyden室化验,伤口愈合试验,RNA测序,本实验采用Westernblot分析。结果表明,三酸抑制ARPE-19细胞的迁移能力。此外,使用RNA测序技术,我们揭示了三酸在ARPE-19细胞中抑制骨形态发生蛋白-6(BMP-6)基因的表达。BMP-6的过表达导致三酸处理的ARPE-19细胞的细胞迁移能力的显著恢复。此外,三酸抑制p38信号通路的磷酸化。此外,阻断p38通路还抑制ARPE-19细胞中BMP-6的表达和迁移。总之,本研究发现,三酸主要通过抑制BMP-6的表达和p38信号通路抑制ARPE-19细胞的迁移。
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