Quercetin Mitigates Inflammatory Responses Induced by Vascular Endothelial Growth Factor in Mouse Retinal Photoreceptor Cells through Suppression of Nuclear Factor Kappa B.
Quercetin Mitigates Inflammatory Responses Induced by Vascular Endothelial Growth Factor in Mouse Retinal Photoreceptor Cells through Suppression of Nuclear Factor Kappa B.
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DOI：
10.3390/ijms18112497
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发表时间：
2017-11-22
影响因子：
5.6
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Lee M;Yun S;Lee H;Yang J
视网膜血管内皮生长因子（VEGF）是眼新生血管性疾病的致病因子。然而，目前还不清楚VEGF如何损伤视网膜神经元。本研究的目的是利用小鼠光感受器来源的细胞证明VEGF调节的炎症蛋白表达以及槲皮素对VEGF诱导的炎症反应的保护作用。免疫印迹和逆转录聚合酶链反应检测蛋白表达、磷酸化和mRNA表达。免疫细胞化学法检测VEGF诱导的细胞界膜降解和核因子κ B（NF-κB）转位。VEGF处理激活了感光细胞中的血管生成信号通路。此外，粘附分子和基质金属蛋白酶在VEGF处理的感光细胞增加。所有这些事件都被槲皮素逆转。槲皮素可恢复VEGF降低的Zona occludins-1和β-catenin。槲皮素可抑制VEGF通过磷酸化丝裂原活化蛋白激酶（MAPK）和蛋白激酶B（Akt）调节的NF-κB信号通路。这些结果表明，槲皮素通过抑制MAPK和Akt使NF-κB信号失活来抑制VEGF诱导的视网膜感光细胞过度炎症反应。这些数据可为开发用于治疗由过量VEGF引起的视网膜疾病的药物或营养品提供基本信息。
Retinal vascular endothelial growth factor (VEGF) increased by neovascularization is well known as a pathogenic factor in ocular neovascular diseases. However, it is still unclear how retinal neurons are damaged by VEGF. The aims of this study are to demonstrate the inflammatory protein expression regulated by VEGF using mouse photoreceptor-derived cells and the protective effect of quercetin against VEGF-induced inflammatory response. Expression and phosphorylation of protein and expression of mRNA were detected by immunoblot and reverse transcriptase polymerase chain reaction. VEGF-induced degradation of limiting membrane and translocation of nuclear factor kappa B (NF-κB) were analyzed by immunocytochemistry. VEGF treatment activated angiogenic signaling pathway in photoreceptor cells. In addition, adhesion molecules and matrix metalloproteinases were increased in VEGF-treated photoreceptor cells. All these events were reversed by quercetin. Zona occludins-1 and β-catenin decreased by VEGF were recovered by quercetin. NF-κB signaling pathway regulated by VEGF through phosphorylations of mitogen-activated protein kinases (MAPK) and protein kinase B (Akt) was suppressed by quercetin. These results suggest that quercetin suppressed VEGF-induced excessive inflammatory response in retinal photoreceptor cells by inactivation of NF-κB signals through inhibition of MAPKs and Akt. These data may provide a basic information for development of pharmaceuticals or nutraceuticals for treatment of retinal diseases caused by excessive VEGF.
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