• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Gαi1 和 Gαi3 介导 VEGF 诱导的 VEGFR2 内吞作用、信号转导和血管生成。

Gαi1 and Gαi3mediate VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.

机构信息

Department of Anesthesiology, Huai'an Maternity and Child Healthcare Hospital, Yangzhou University Medical School, Huai'an, China.

The Fourth School of Clinical Medicine, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210029, China.

出版信息

Theranostics. 2018 Sep 9;8(17):4695-4709. doi: 10.7150/thno.26203. eCollection 2018.

DOI:10.7150/thno.26203
PMID:30279732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6160771/
Abstract

VEGF binding to VEGFR2 leads to VEGFR2 endocytosis and downstream signaling activation to promote angiogenesis. Using genetic strategies, we tested the requirement of α subunits of heterotrimeric G proteins (Gαi1/3) in the process. Gαi1/3 are located in the VEGFR2 endocytosis complex (VEGFR2-Ephrin-B2-Dab2-PAR-3), where they are required for VEGFR2 endocytosis and downstream signaling transduction. Gαi1/3 knockdown, knockout or dominant negative mutation inhibited VEGF-induced VEGFR2 endocytosis, and downstream Akt-mTOR and Erk-MAPK activation. Functional studies show that Gαi1/3 shRNA inhibited VEGF-induced proliferation, invasion, migration and vessel-like tube formation of HUVECs. , Gαi1/3 shRNA lentivirus inhibited alkali burn-induced neovascularization in mouse cornea. Further, oxygen-induced retinopathy (OIR)-induced retinal neovascularization was inhibited by intravitreal injection of Gαi1/3 shRNA lentivirus. Moreover, angiogenesis by alkali burn and OIR was significantly attenuated in Gαi1/3 double knockout mice. Significantly, Gαi1/3 proteins are upregulated in proliferative retinal tissues of proliferative diabetic retinopathy (PDR) patients. These results provide mechanistic insights into the critical role played by Gαi1/3 proteins in VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.

摘要

VEGF 与 VEGFR2 的结合导致 VEGFR2 内吞作用和下游信号激活，从而促进血管生成。我们使用遗传策略测试了异三聚体 G 蛋白（Gαi1/3）的α亚基在该过程中的需求。Gαi1/3 位于 VEGFR2 内吞复合物（VEGFR2-Ephrin-B2-Dab2-PAR-3）中，在该复合物中，它们是 VEGFR2 内吞作用和下游信号转导所必需的。Gαi1/3 的敲低、敲除或显性负突变抑制了 VEGF 诱导的 VEGFR2 内吞作用，以及下游 Akt-mTOR 和 Erk-MAPK 的激活。功能研究表明，Gαi1/3 shRNA 抑制了 VEGF 诱导的 HUVECs 的增殖、侵袭、迁移和管状结构形成。Gαi1/3 shRNA 慢病毒抑制了小鼠角膜碱烧伤诱导的新生血管形成。此外，玻璃体内注射 Gαi1/3 shRNA 慢病毒抑制了氧诱导的视网膜病变（OIR）诱导的视网膜新生血管形成。此外，在 Gαi1/3 双敲除小鼠中，碱烧伤和 OIR 引起的血管生成明显减弱。重要的是，在增生性糖尿病视网膜病变（PDR）患者的增生性视网膜组织中，Gαi1/3 蛋白上调。这些结果为 Gαi1/3 蛋白在 VEGF 诱导的 VEGFR2 内吞作用、信号转导和血管生成中的关键作用提供了机制上的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/fd39a78592cb/thnov08p4695g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/3e29bd3b9930/thnov08p4695g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/cb9940c4584a/thnov08p4695g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/8b1eb6707c5e/thnov08p4695g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/e9c623d48203/thnov08p4695g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/d5f8228c30ab/thnov08p4695g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/8fb79ead3319/thnov08p4695g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/fd39a78592cb/thnov08p4695g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/3e29bd3b9930/thnov08p4695g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/cb9940c4584a/thnov08p4695g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/8b1eb6707c5e/thnov08p4695g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/e9c623d48203/thnov08p4695g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/d5f8228c30ab/thnov08p4695g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/8fb79ead3319/thnov08p4695g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9de5/6160771/fd39a78592cb/thnov08p4695g007.jpg

相似文献

1
Gαi1 and Gαi3mediate VEGF-induced VEGFR2 endocytosis, signaling and angiogenesis.Gαi1 和 Gαi3 介导 VEGF 诱导的 VEGFR2 内吞作用、信号转导和血管生成。
Theranostics. 2018 Sep 9;8(17):4695-4709. doi: 10.7150/thno.26203. eCollection 2018.
2
Syntenin promotes VEGF-induced VEGFR2 endocytosis and angiogenesis by increasing ephrin-B2 function in endothelial cells.Syntenin通过增强内皮细胞中ephrin-B2的功能来促进VEGF诱导的VEGFR2内吞作用和血管生成。
Oncotarget. 2017 Jun 13;8(24):38886-38901. doi: 10.18632/oncotarget.16452.
3
SCF/c-Kit-activated signaling and angiogenesis require Gαi1 and Gαi3.SCF/c-Kit 激活的信号转导和血管生成需要 Gαi1 和 Gαi3。
Int J Biol Sci. 2023 Mar 27;19(6):1910-1924. doi: 10.7150/ijbs.82855. eCollection 2023.
4
Gαi1/3 mediate Netrin-1-CD146-activated signaling and angiogenesis.Gαi1/3 介导轴突导向因子 Netrin-1-CD146 激活的信号通路和血管生成。
Theranostics. 2023 Apr 17;13(7):2319-2336. doi: 10.7150/thno.80749. eCollection 2023.
5
Loss of osteoglycin promotes angiogenesis in limb ischaemia mouse models via modulation of vascular endothelial growth factor and vascular endothelial growth factor receptor 2 signalling pathway.骨连蛋白缺失通过调节血管内皮生长因子和血管内皮生长因子受体 2 信号通路促进肢体缺血小鼠模型中的血管生成。
Cardiovasc Res. 2017 Jan;113(1):70-80. doi: 10.1093/cvr/cvw220. Epub 2016 Oct 23.
6
The interaction of uPAR with VEGFR2 promotes VEGF-induced angiogenesis.尿激酶型纤溶酶原激活物受体（uPAR）与血管内皮生长因子受体2（VEGFR2）的相互作用促进了血管内皮生长因子（VEGF）诱导的血管生成。
Sci Signal. 2015 Nov 17;8(403):ra117. doi: 10.1126/scisignal.aaa2403.
7
Necl-5/poliovirus receptor interacts with VEGFR2 and regulates VEGF-induced angiogenesis.Necl-5/poliovirus 受体与 VEGFR2 相互作用，调节 VEGF 诱导的血管生成。
Circ Res. 2012 Mar 2;110(5):716-26. doi: 10.1161/CIRCRESAHA.111.256834. Epub 2012 Jan 26.
8
Endothelial SCUBE2 Interacts With VEGFR2 and Regulates VEGF-Induced Angiogenesis.内皮细胞SCUBE2与血管内皮生长因子受体2相互作用并调节血管内皮生长因子诱导的血管生成。
Arterioscler Thromb Vasc Biol. 2017 Jan;37(1):144-155. doi: 10.1161/ATVBAHA.116.308546. Epub 2016 Nov 10.
9
Total Flavones of Abelmoschus manihot Exhibits Pro-Angiogenic Activity by Activating the VEGF-A/VEGFR2-PI3K/Akt Signaling Axis.黄蜀葵花总黄酮通过激活 VEGF-A/VEGFR2-PI3K/Akt 信号通路发挥促血管生成活性。
Am J Chin Med. 2018;46(3):567-583. doi: 10.1142/S0192415X18500295. Epub 2018 Mar 29.
10
Cryptotanshinone inhibits VEGF-induced angiogenesis by targeting the VEGFR2 signaling pathway.隐丹参酮通过靶向血管内皮生长因子受体2（VEGFR2）信号通路抑制血管内皮生长因子（VEGF）诱导的血管生成。
Microvasc Res. 2017 May;111:25-31. doi: 10.1016/j.mvr.2016.12.011. Epub 2016 Dec 28.

引用本文的文献

1
Gap junction protein beta 5 interacts with Gαi3 to promote Akt activation and cervical cancer cell growth.缝隙连接蛋白β5与Gαi3相互作用以促进Akt激活和宫颈癌细胞生长。
Cell Death Dis. 2025 Jun 19;16(1):461. doi: 10.1038/s41419-025-07768-w.
2
Gαi3: a crucial biomarker and therapeutic target in bladder cancer.Gαi3：膀胱癌中的关键生物标志物和治疗靶点。
NPJ Precis Oncol. 2025 Jun 13;9(1):181. doi: 10.1038/s41698-025-00989-4.
3
Potential mechanisms of epigenetic regulation in diabetic retinopathy from the perspectives of multi-omics.

本文引用的文献

1
Itraconazole-Induced Inhibition on Human Esophageal Cancer Cell Growth Requires AMPK Activation.伊曲康唑通过激活 AMPK 抑制人食管癌细胞生长。
Mol Cancer Ther. 2018 Jun;17(6):1229-1239. doi: 10.1158/1535-7163.MCT-17-1094. Epub 2018 Mar 28.
2
Inhibition of HHIP Promoter Methylation Suppresses Human Gastric Cancer Cell Proliferation and Migration.抑制HHIP启动子甲基化可抑制人胃癌细胞的增殖和迁移。
Cell Physiol Biochem. 2018;45(5):1840-1850. doi: 10.1159/000487875. Epub 2018 Feb 28.
3
microRNA-200a downregulation in human glioma leads to Gαi1 over-expression, Akt activation, and cell proliferation.
从多组学角度看糖尿病视网膜病变中表观遗传调控的潜在机制
Diabetol Metab Syndr. 2025 May 14;17(1):155. doi: 10.1186/s13098-025-01723-7.
4
OPN3-mediated positive regulation of angiogenesis in HUVECs through VEGFR2 interaction.OPN3通过与VEGFR2相互作用对人脐静脉内皮细胞（HUVECs）血管生成进行正向调控。
Commun Biol. 2025 Mar 31;8(1):529. doi: 10.1038/s42003-025-07958-4.
5
Gαi1/3 signaling mediates IL-5-induced eosinophil activation and type 2 inflammation in eosinophilic chronic rhinosinusitis.Gαi1/3信号传导介导白细胞介素-5诱导的嗜酸性粒细胞活化及嗜酸性慢性鼻-鼻窦炎中的2型炎症。
Front Immunol. 2025 Jan 7;15:1460104. doi: 10.3389/fimmu.2024.1460104. eCollection 2024.
6
Identification of Gαi3 as a promising molecular oncotarget of pancreatic cancer.鉴定 Gαi3 为胰腺癌有前景的分子治疗靶点。
Cell Death Dis. 2024 Sep 30;15(9):699. doi: 10.1038/s41419-024-07079-6.
7
The critical role of Gαi3 in oral squamous cell carcinoma cell growth.Gαi3在口腔鳞状细胞癌细胞生长中的关键作用。
Cell Death Discov. 2024 Oct 1;10(1):420. doi: 10.1038/s41420-024-02191-0.
8
Exploitation of enhanced prime editing for blocking aberrant angiogenesis.利用增强型碱基编辑技术阻断异常血管生成。
J Adv Res. 2025 Jun;72:121-133. doi: 10.1016/j.jare.2024.07.006. Epub 2024 Jul 10.
9
Identification of the central role of RNA polymerase mitochondrial for angiogenesis.鉴定 RNA 聚合酶线粒体在血管生成中的核心作用。
Cell Commun Signal. 2024 Jun 21;22(1):343. doi: 10.1186/s12964-024-01712-9.
10
Targeting the mitochondrial protein YME1L to inhibit osteosarcoma cell growth in vitro and in vivo.靶向线粒体蛋白 YME1L 抑制骨肉瘤细胞在体外和体内的生长。
Cell Death Dis. 2024 May 20;15(5):346. doi: 10.1038/s41419-024-06722-6.
microRNA-200a 在人脑胶质瘤中的下调导致 Gαi1 过表达、Akt 激活和细胞增殖。
Oncogene. 2018 May;37(21):2890-2902. doi: 10.1038/s41388-018-0184-5. Epub 2018 Mar 9.
4
Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus.BDNF 的抗抑郁作用需要 Gαi1/3 在海马中的表达，并被其模拟。
Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):E3549-E3558. doi: 10.1073/pnas.1722493115. Epub 2018 Mar 5.
5
Ginsenoside Rh2 inhibits vascular endothelial growth factor-induced corneal neovascularization.人参皂苷 Rh2 抑制血管内皮生长因子诱导的角膜新生血管形成。
FASEB J. 2018 Jul;32(7):3782-3791. doi: 10.1096/fj.201701074RR. Epub 2018 Feb 20.
6
Silencing Of Circular RNA-ZNF609 Ameliorates Vascular Endothelial Dysfunction.环状RNA-ZNF609的沉默改善血管内皮功能障碍。
Theranostics. 2017 Jul 8;7(11):2863-2877. doi: 10.7150/thno.19353. eCollection 2017.
7
Gαi3 nuclear translocation causes irradiation resistance in human glioma cells.Gαi3核转位导致人胶质瘤细胞的辐射抗性。
Oncotarget. 2017 May 23;8(21):35061-35068. doi: 10.18632/oncotarget.17043.
8
Syntenin promotes VEGF-induced VEGFR2 endocytosis and angiogenesis by increasing ephrin-B2 function in endothelial cells.Syntenin通过增强内皮细胞中ephrin-B2的功能来促进VEGF诱导的VEGFR2内吞作用和血管生成。
Oncotarget. 2017 Jun 13;8(24):38886-38901. doi: 10.18632/oncotarget.16452.
9
mTOR Signaling in Growth, Metabolism, and Disease.生长、代谢及疾病中的mTOR信号传导
Cell. 2017 Mar 9;168(6):960-976. doi: 10.1016/j.cell.2017.02.004.
10
VEGF induces signalling and angiogenesis by directing VEGFR2 internalisation through macropinocytosis.血管内皮生长因子（VEGF）通过巨胞饮作用引导血管内皮生长因子受体2（VEGFR2）内化，从而诱导信号传导和血管生成。
J Cell Sci. 2016 Nov 1;129(21):4091-4104. doi: 10.1242/jcs.188219. Epub 2016 Sep 21.