Purpose

We previously found the mutation frequency of cytoskeleton-associated protein 2 (CKAP2) was significantly increased in proliferative diabetic retinopathy (PDR) patients through whole exome sequencing. The present study was conducted to explore the expression and possible mechanism of CKAP2 in PDR patients and human retinal capillary endothelial cells (HRCECs) under high-glucose (HG) conditions.

Methods

Expression of CKAP2 and p53 in the vitreous fluid and fibrovascular membrane (FVM) of PDR patients and HRCECs under HG conditions was observed. Cell proliferation, migration and tubule formation were assessed. Ranibizumab and siRNA transfection were used in the inhibition assay.

Results

CKAP2 and p53 were significantly increased in the ocular tissues of PDR patients. HG combined with VEGF treatment significantly up-regulated expression of CKAP2 and p53 in HRCECs. Inhibition of CKAP2 attenuated the abilities of cell proliferation, migration and tube formation under HG conditions. Blocking VEGF or p53 significantly decreased CKAP2 expression, whereas inhibition of CKAP2 failed to alter the level of VEGF or p53.

Conclusions

CKAP2 is involved in the pathogenesis of PDR and regulated by VEGF and p53 under HG conditions.

中文翻译：

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在高糖条件下，细胞骨架相关蛋白 2 (CKAP2) 受视网膜毛细血管内皮细胞中血管内皮生长因子和 p53 的调节

目的

我们之前通过全外显子组测序发现增殖性糖尿病视网膜病变 (PDR) 患者的细胞骨架相关蛋白 2 (CKAP2) 的突变频率显着增加。本研究旨在探讨高糖（HG）条件下CKAP2在PDR患者和人视网膜毛细血管内皮细胞（HRCECs）中的表达及其可能机制。

方法

观察 HG 条件下 PDR 患者和 HRCECs 玻璃体液和纤维血管膜 (FVM) 中 CKAP2 和 p53 的表达。评估细胞增殖、迁移和小管形成。雷珠单抗和 siRNA 转染用于抑制测定。

结果

PDR患者的眼组织中CKAP2和p53显着增加。HG 联合 VEGF 治疗显着上调 HRCECs 中 CKAP2 和 p53 的表达。CKAP2的抑制减弱了HG条件下细胞增殖、迁移和管形成的能力。阻断 VEGF 或 p53 显着降低 CKAP2 表达，而抑制 CKAP2 未能改变 VEGF 或 p53 的水平。

结论

CKAP2 参与 PDR 的发病机制，并在 HG 条件下受 VEGF 和 p53 的调节。