SENP6-Mediated deSUMOylation of VEGFR2 Enhances Its Cell Membrane Transport in Angiogenesis.
SENP6-Mediated deSUMOylation of VEGFR2 Enhances Its Cell Membrane Transport in Angiogenesis.
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SENP6 介导的 VEGFR2 去SUMO化增强其在血管生成中的细胞膜运输
DOI：
10.3390/ijms24032544
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发表时间：
2023-01-29
影响因子：
5.6
通讯作者：
Guo, Xiaohua
中科院分区：
文献类型：
--
作者：
He, Qi;Chen, Zhenfeng;Li, Jieyu;Liu, Jinlian;Zuo, Zirui;Lin, Bingqi;Song, Ke;Zhou, Chuyu;Lai, Haipeng;Huang, Qiaobing;Guo, Xiaohua
血管生成是糖尿病微血管病变的重要病理特征。晚期糖基化终产物（AGEs）在糖尿病组织中显著升高，并可影响血管内皮细胞的形状和功能。血管内皮生长因子（VEGF）-VEGF受体2（VEGFR 2）信号通路的调节是血管生成调节中的关键机制，并且VEGFR 2活性可以通过翻译后变化来修饰。然而，很少有研究已经进行了控制小泛素相关修饰剂（SUMO）介导的VEGFR 2的变化。目前的研究使用人脐静脉内皮细胞（HUVECs）结合免疫印迹和免疫荧光法对此进行了研究。AGEs可增加Nrf 2向细胞核的转运，促进VEGFR 2的表达。它们还增加了sentrin/SUMO特异性蛋白酶6（SENP 6）的表达，该蛋白酶6使VEGFR 2去SUMO化，免疫荧光表明高尔基体中VEGFR 2积累减少，并增加了VEGFR 2通过外被体蛋白复合物亚基β 2从高尔基体转运至细胞膜表面。细胞膜上的VEGFR 2与周细胞产生的VEGF连接，触发VEGF信号级联反应。总之，这项研究表明，SENP 6调节VEGFR 2从高尔基体运输到内皮细胞表面。SENP 6-VEGFR 2通路在病理性血管生成中起关键作用。
Angiogenesis is a significant pathogenic characteristic of diabetic microangiopathy. Advanced glycation end products (AGEs) are considerably elevated in diabetic tissues and can affect vascular endothelial cell shape and function. Regulation of the vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) signaling pathway is a critical mechanism in the regulation of angiogenesis, and VEGFR2 activity can be modified by post-translational changes. However, little research has been conducted on the control of small ubiquitin-related modifier (SUMO)-mediated VEGFR2 alterations. The current study investigated this using human umbilical vein endothelial cells (HUVECs) in conjunction with immunoblotting and immunofluorescence. AGEs increased Nrf2 translocation to the nucleus and promoted VEGFR2 expression. They also increased the expression of sentrin/SUMO-specific protease 6 (SENP6), which de-SUMOylated VEGFR2, and immunofluorescence indicated a reduction in VEGFR2 accumulation in the Golgi and increased VEGFR2 transport from the Golgi to the cell membrane surface via the coatomer protein complex subunit beta 2. VEGFR2 on the cell membrane was linked to VEGF generated by pericytes, triggering the VEGF signaling cascade. In conclusion, this study demonstrates that SENP6 regulates VEGFR2 trafficking from the Golgi to the endothelial cell surface. The SENP6-VEGFR2 pathway plays a critical role in pathological angiogenesis.
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