Normal vitreous promotes angiogenesis via activation of Axl
Normal vitreous promotes angiogenesis via activation of Axl
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正常玻璃体通过 Axl 激活促进血管生成
DOI：
10.1096/fj.201903105r
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发表时间：
2020-11-05
期刊：
影响因子：
4.8
通讯作者：
Lei, Hetian
中科院分区：
文献类型：
--
作者：
Wu, Wenyi;Xia, Xiaobo;Lei, Hetian
据报道，玻璃体可以预防肿瘤血管生成，但我们之前的研究结果表明，玻璃体激活磷酸肌醇 3-激酶 (PI3K)/Akt 信号通路，该信号通路在血管生成中发挥关键作用。本研究的目的是确定玻璃体在体外血管生成相关细胞反应中发挥的作用。我们发现，在人视网膜微血管内皮细胞 (HREC) 中，玻璃体激活许多受体酪氨酸激酶，包括 Anexelekto (Axl)，它在血管生成中发挥重要作用。随后，我们发现使用 CRISPR/Cas9 和 Axl 特异性抑制剂 R428 消除 Axl 可抑制玻璃体诱导的 Akt 激活以及 HREC 的细胞增殖、迁移和块茎形成。因此，该研究不仅证明了玻璃体在体外促进血管生成，而且揭示了Axl是体外介导玻璃体诱导血管生成的受体酪氨酸激酶之一，从而为增殖性糖尿病视网膜病变患者进行玻璃体切除术时尽可能干净地切除玻璃体提供了分子基础。
Vitreous has been reported to prevent tumor angiogenesis, but our previous findings indicate that vitreous activate the signaling pathway of phosphoinositide 3-kinase (PI3K)/Akt, which plays a critical role in angiogenesis. The goal of this research is to determine which role of vitreous plays in angiogenesis-related cellular responses in vitro. We found that in human retinal microvascular endothelial cells (HRECs) vitreous activates a number of receptor tyrosine kinases including Anexelekto (Axl), which plays an important role in angiogenesis. Subsequently, we discovered that depletion of Axl using CRISPR/Cas9 and an Axl-specific inhibitor R428 suppress vitreous-induced Akt activation and cell proliferation, migration, and tuber formation of HRECs. Therefore, this line of research not only demonstrate that vitreous promotes angiogenesis in vitro, but also reveal that Axl is one of receptor tyrosine kinases to mediate vitreous-induced angiogenesis in vitro, thereby providing a molecular basis for removal of vitreous as cleanly as possible when vitrectomy is performed in treating patients with proliferative diabetic retinopathy.