Puerarin suppresses hypoxia-induced vascular endothelial growth factor upregulation in human retinal pigmented epithelial cells by blocking JAK2/STAT3 pathway

葛根素通过阻断JAK2/STAT3通路抑制人视网膜色素上皮细胞中缺氧诱导的血管内皮生长因子上调。

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Abstract

The purpose of this study was to explore the mechanism by which puerarin regulated the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) in humans' retinal pigment epithelial (RPE) cells under hypoxia. RPE cells (ARPE-19 and D407 cells) and a rat model of oxygen-induced retinopathy were used in the current study. Western blotting and ELISA were performed to detect the level of JAK2, phosphorylated JAK2, STAT3, phosphorylated STAT3, HIF-1α, and VEGF in cells. In addition, the interaction between JAK2 and STAT3 was determined using with a co-immunoprecipitation assay. We found puerarin inhibited hypoxia-induced upregulation of VEGF at both the mRNA and protein level via decreasing HIF-1α expression in RPE cells. Moreover, puerarin attenuated the interaction between JAK2 and STAT3, and subsequently blocking p-STAT3 nucleus translocation in vitro and in vivo. In conclusion, puerarin could effectively inhibit hypoxia-induced VEGF upregulation in RPE cells via mediated JAK2/STAT3 pathway.

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