RKIP negatively regulates the glucose induced angiogenesis and endothelial-mesenchymal transition in retinal endothelial cells
RKIP negatively regulates the glucose induced angiogenesis and endothelial-mesenchymal transition in retinal endothelial cells
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RKIP 负向调节视网膜内皮细胞中葡萄糖诱导的血管生成和内皮间质转化
DOI：
10.1016/j.exer.2019.107851
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发表时间：
2019-12-01
影响因子：
3.4
通讯作者：
Wang, Fang
中科院分区：
文献类型：
--
作者：
Feng, Le;Zhang, Conghui;Wang, Fang
糖尿病视网膜病变（DR）是糖尿病常见的微血管并发症，据报道是世界范围内致盲的主要原因。我们在前期的研究中发现，增殖型糖尿病视网膜病变（proliferative diabetic retinopathy，PDR）患者玻璃体液中Raf激酶抑制蛋白（Raf kinase inhibitor protein，RKIP）表达明显减少，提示RKIP可能在PDR的发生发展中起一定作用。为了研究RKIP在PDR中的作用，通过使用慢病毒构建体在人视网膜毛细血管内皮细胞（HRCEC）中产生RKIP的稳定过表达和敲低。然后，葡萄糖诱导的细胞活力，迁移，血管生成，和（内皮细胞间质转化）EndMT在RKIP全型（WT），敲低（KD）和过表达（OE）HRCEC。结果显示，与RKIP-WT组相比，RKIP-KD组葡萄糖诱导的细胞活力、迁移能力和血管生成能力显著增强，而RKIP-OE组葡萄糖诱导的细胞活力、迁移能力和血管生成能力显著降低。与对照组相比，RKIP-KD组CD 31、vWF表达上调，α-SMA表达下调; RKIP-OE组CD 31、vWF表达下调，α-SMA表达上调。总之，我们的研究结果表明，RKIP负调节葡萄糖诱导的细胞活力，迁移，血管生成，并在HRCEC的EndMT，这表明在PDR患者的玻璃体液中的RKIP的下调可能有助于DR的发展。
Diabetic retinopathy (DR), a common microvascular complication of diabetes, is reported to be the leading cause of blindness worldwide. In our previous study, we found that the Raf kinase inhibitor protein (RKIP) is significantly decreased in vitreous humor of proliferative diabetic retinopathy (PDR) patients, which indicated that RKIP might play a role in the development of PDR. To investigate the role of RKIP in PDR, stable overexpression and knockdown of RKIP in Human retinal capillary endothelial cells (HRCECs) were generated by using lenti-virus constructs. Then, the glucose-induced cell viability, migration, angiogenesis, and (endothelial to mesenchymal transition) EndMT were determined in the RKIP-wide type (WT), -knocking down (KD) and -over-expression (OE) HRCECs. The results showed that, compared with the RKIP-WT groups, the glucose-induced cell viabilities, migration and angiogenesis were significantly increased in the RKIP-KD groups, while significantly decreased in the RKIP-OE groups. Besides, compared with the control groups, CD31 and vWF were upregulated, while alpha-SMA was downregulated in the RKIP-KD groups, while CD31 and vWF were downregulated, while alpha-SMA was upregulated in the RKIP-OE groups induced by glucose. In conclusion, our results showed that RKIP negatively regulates glucose-induced cell viability, migration, angiogenesis, and EndMT in HRCECs, suggesting that the downregulation of RKIP in the vitreous humor of PDR patients might contribute to the development of DR.