• 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

内皮细胞衍生的 RSPO3 通过激活 Gαi1/3-Erk 信号通路保护神经元免受缺血再灌注损伤。

Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury.

机构信息

Shandong University, Department of Neurology, Shandong Provincial Hospital, Jinan, China.

Department of Neurology, Shouguang Hospital of T.C.M, Shouguang, China.

出版信息

Cell Death Dis. 2023 Oct 7;14(10):654. doi: 10.1038/s41419-023-06176-2.

DOI:10.1038/s41419-023-06176-2
PMID:37805583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10560285/
Abstract

The current study explores the potential function and the underlying mechanisms of endothelial cell-derived R-spondin 3 (RSPO3) neuroprotection against ischemia/reperfusion-induced neuronal cell injury. In both neuronal cells (Neuro-2a) and primary murine cortical neurons, pretreatment with RSPO3 ameliorated oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced neuronal cell death and oxidative injury. In neurons RSPO3 activated the Akt, Erk and β-Catenin signaling cascade, but only Erk inhibitors reversed RSPO3-induced neuroprotection against OGD/R. In mouse embryonic fibroblasts (MEFs) and neuronal cells, RSPO3-induced LGR4-Gab1-Gαi1/3 association was required for Erk activation, and either silencing or knockout of Gαi1 and Gαi3 abolished RSPO3-induced neuroprotection. In mice, middle cerebral artery occlusion (MCAO) increased RSPO3 expression and Erk activation in ischemic penumbra brain tissues. Endothelial knockdown or knockout of RSPO3 inhibited Erk activation in the ischemic penumbra brain tissues and increased MCAO-induced cerebral ischemic injury in mice. Conversely, endothelial overexpression of RSPO3 ameliorated MCAO-induced cerebral ischemic injury. We conclude that RSPO3 activates Gαi1/3-Erk signaling to protect neuronal cells from ischemia/reperfusion injury.

摘要

本研究探讨了内皮细胞衍生的 R- 脊椎蛋白 3（RSPO3）对缺血/再灌注诱导的神经元细胞损伤的神经保护作用及其潜在机制。在神经元细胞（Neuro-2a）和原代小鼠皮质神经元中，RSPO3 预处理可改善氧葡萄糖剥夺（OGD）/复氧（OGD/R）诱导的神经元细胞死亡和氧化损伤。在神经元中，RSPO3 激活 Akt、Erk 和 β-连环蛋白信号级联，但只有 Erk 抑制剂可逆转 RSPO3 诱导的对 OGD/R 的神经保护作用。在小鼠胚胎成纤维细胞（MEFs）和神经元细胞中，RSPO3 诱导的 LGR4-Gab1-Gαi1/3 缔合是 Erk 激活所必需的，而 Gαi1 和 Gαi3 的沉默或敲除则消除了 RSPO3 诱导的神经保护作用。在小鼠中，大脑中动脉闭塞（MCAO）增加了缺血半影脑组织中 RSPO3 的表达和 Erk 的激活。内皮细胞 RSPO3 的敲低或敲除抑制了缺血半影脑组织中的 Erk 激活，并增加了 MCAO 诱导的小鼠脑缺血损伤。相反，内皮细胞 RSPO3 的过表达改善了 MCAO 诱导的脑缺血损伤。我们的结论是，RSPO3 通过激活 Gαi1/3-Erk 信号通路来保护神经元细胞免受缺血/再灌注损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/904fe700a5c3/41419_2023_6176_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/bb0fd5489659/41419_2023_6176_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/742421d1cea3/41419_2023_6176_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/84efd1a51b56/41419_2023_6176_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/82a7874f2296/41419_2023_6176_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/7f8b400c2590/41419_2023_6176_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/c1b4dcdabd9c/41419_2023_6176_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/83d5e5405fd8/41419_2023_6176_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/878de230897c/41419_2023_6176_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/f9a64532e954/41419_2023_6176_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/904fe700a5c3/41419_2023_6176_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/bb0fd5489659/41419_2023_6176_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/742421d1cea3/41419_2023_6176_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/84efd1a51b56/41419_2023_6176_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/82a7874f2296/41419_2023_6176_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/7f8b400c2590/41419_2023_6176_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/c1b4dcdabd9c/41419_2023_6176_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/83d5e5405fd8/41419_2023_6176_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/878de230897c/41419_2023_6176_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/f9a64532e954/41419_2023_6176_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fe/10560285/904fe700a5c3/41419_2023_6176_Fig10_HTML.jpg

相似文献

1
Endothelial cell-derived RSPO3 activates Gαi1/3-Erk signaling and protects neurons from ischemia/reperfusion injury.内皮细胞衍生的 RSPO3 通过激活 Gαi1/3-Erk 信号通路保护神经元免受缺血再灌注损伤。
Cell Death Dis. 2023 Oct 7;14(10):654. doi: 10.1038/s41419-023-06176-2.
2
Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.神经元分泌的 NLGN3 通过激活 Gαi1/3-Akt 信号转导来减轻缺血性脑损伤。
Cell Death Dis. 2023 Oct 25;14(10):700. doi: 10.1038/s41419-023-06219-8.
3
Silencing PAQR3 protects against oxygen-glucose deprivation/reperfusion-induced neuronal apoptosis via activation of PI3K/AKT signaling in PC12 cells.沉默 PAQR3 通过激活 PC12 细胞中的 PI3K/AKT 信号通路来防止氧葡萄糖剥夺/再灌注诱导的神经元凋亡。
Life Sci. 2021 Jan 15;265:118806. doi: 10.1016/j.lfs.2020.118806. Epub 2020 Nov 26.
4
[PI3K/Akt/Erk signaling pathway mediates neuroprotection of CaMKⅡγ and CaMKⅡδ against ischemic reperfusion injury in mice].[PI3K/Akt/Erk信号通路介导CaMKⅡγ和CaMKⅡδ对小鼠缺血再灌注损伤的神经保护作用]
Nan Fang Yi Ke Da Xue Xue Bao. 2024 Mar 20;44(3):563-570. doi: 10.12122/j.issn.1673-4254.2024.03.18.
5
R-spondin 3/LGR4 (Leucine-Rich Repeat-Containing G Protein-Coupled Receptor 4) Axis Is a Novel Inflammatory and Neurite Outgrowth Signaling System in the Ischemic Brain in Mice.R -spondin 3/LGR4（富含亮氨酸重复序列的 G 蛋白偶联受体 4）轴是小鼠缺血性脑内新的炎症和神经突生长信号系统。
Stroke. 2023 Jun;54(6):1606-1615. doi: 10.1161/STROKEAHA.122.041970. Epub 2023 May 11.
6
MiR-342-5p protects neurons from cerebral ischemia induced-apoptosis through regulation of Akt/NF-κB pathways by targeting CCAR2.微小RNA-342-5p通过靶向细胞周期和凋亡调节因子2调控Akt/核因子-κB信号通路，从而保护神经元免受脑缺血诱导的细胞凋亡。
J Stroke Cerebrovasc Dis. 2023 Jan;32(1):106901. doi: 10.1016/j.jstrokecerebrovasdis.2022.106901. Epub 2022 Nov 23.
7
Down-regulation of microRNA-142-5p attenuates oxygen-glucose deprivation and reoxygenation-induced neuron injury through up-regulating Nrf2/ARE signaling pathway.下调 microRNA-142-5p 通过上调 Nrf2/ARE 信号通路减轻氧葡萄糖剥夺复氧诱导的神经元损伤。
Biomed Pharmacother. 2017 May;89:1187-1195. doi: 10.1016/j.biopha.2017.03.011. Epub 2017 Mar 14.
8
PAQR3 protects against oxygen-glucose deprivation/reperfusion-induced injury through the ERK signaling pathway in N2A cells.PAQR3 通过 ERK 信号通路保护 N2A 细胞免受氧葡萄糖剥夺/再灌注诱导的损伤。
J Mol Histol. 2020 Jun;51(3):307-315. doi: 10.1007/s10735-020-09881-w. Epub 2020 May 25.
9
Inhibition of miR-19a-3p decreases cerebral ischemia/reperfusion injury by targeting IGFBP3 in vivo and in vitro.体内外抑制 miR-19a-3p 通过靶向 IGFBP3 减少脑缺血/再灌注损伤。
Biol Res. 2020 Apr 20;53(1):17. doi: 10.1186/s40659-020-00280-9.
10
Long Non-coding RNA PVT1 Inhibits miR-30c-5p to Upregulate Rock2 to Modulate Cerebral Ischemia/Reperfusion Injury Through MAPK Signaling Pathway Activation.长链非编码RNA PVT1通过激活MAPK信号通路抑制miR-30c-5p上调Rock2来调节脑缺血/再灌注损伤。
Mol Neurobiol. 2021 Nov;58(11):6032-6048. doi: 10.1007/s12035-021-02539-y. Epub 2021 Aug 26.

引用本文的文献

1
Regulation of placental development and function by ubiquitination.泛素化对胎盘发育和功能的调控
Mol Med. 2025 May 23;31(1):202. doi: 10.1186/s10020-025-01268-5.
2
Neural Responses to Hypoxic Injury in a Vascularized Cerebral Organoid Model.血管化脑类器官模型中对缺氧损伤的神经反应
Neurosci Bull. 2025 Apr 22. doi: 10.1007/s12264-025-01396-2.
3
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。

本文引用的文献

1
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.
2
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.
3
YME1L overexpression exerts pro-tumorigenic activity in glioma by promoting Gαi1 expression and Akt activation.
Cell Death Discov. 2024 Oct 1;10(1):420. doi: 10.1038/s41420-024-02191-0.
4
G protein subunit alpha i2's pivotal role in angiogenesis.G 蛋白亚单位 α i2 在血管生成中的关键作用。
Theranostics. 2024 Mar 3;14(5):2190-2209. doi: 10.7150/thno.92909. eCollection 2024.
5
Neuron-secreted NLGN3 ameliorates ischemic brain injury via activating Gαi1/3-Akt signaling.神经元分泌的 NLGN3 通过激活 Gαi1/3-Akt 信号转导来减轻缺血性脑损伤。
Cell Death Dis. 2023 Oct 25;14(10):700. doi: 10.1038/s41419-023-06219-8.
YME1L过表达通过促进Gαi1表达和Akt激活在胶质瘤中发挥促肿瘤活性。
Protein Cell. 2023 Apr 13;14(3):223-229. doi: 10.1093/procel/pwac011.
4
Gαi1/3 mediation of Akt-mTOR activation is important for RSPO3-induced angiogenesis.Gαi1/3介导的Akt-mTOR激活对RSPO3诱导的血管生成很重要。
Protein Cell. 2023 Apr 13;14(3):217-222. doi: 10.1093/procel/pwac035.
5
TIMM44 is a potential therapeutic target of human glioma.TIMM44 是人类脑胶质瘤的一个潜在治疗靶点。
Theranostics. 2022 Oct 31;12(17):7586-7602. doi: 10.7150/thno.78616. eCollection 2022.
6
Simple and efficient protocol to isolate and culture brain microvascular endothelial cells from newborn mice.从新生小鼠中分离和培养脑微血管内皮细胞的简单高效方法。
Front Cell Neurosci. 2022 Oct 13;16:949412. doi: 10.3389/fncel.2022.949412. eCollection 2022.
7
Mitochondrial ferritin alleviates apoptosis by enhancing mitochondrial bioenergetics and stimulating glucose metabolism in cerebral ischemia reperfusion.线粒体铁蛋白通过增强线粒体生物能量学和刺激脑缺血再灌注中的葡萄糖代谢来减轻细胞凋亡。
Redox Biol. 2022 Nov;57:102475. doi: 10.1016/j.redox.2022.102475. Epub 2022 Sep 24.
8
The requirement of phosphoenolpyruvate carboxykinase 1 for angiogenesis in vitro and in vivo.体外和体内血管生成中磷酸烯醇丙酮酸羧激酶1的需求
Sci Adv. 2022 May 27;8(21):eabn6928. doi: 10.1126/sciadv.abn6928.
9
Construction of PLGA/JNK3-shRNA nanoparticles and their protective role in hippocampal neuron apoptosis induced by oxygen and glucose deprivation.聚乳酸-羟基乙酸共聚物/ JNK3小干扰RNA纳米粒的构建及其在氧糖剥夺诱导的海马神经元凋亡中的保护作用
RSC Adv. 2018 Jun 1;8(36):20108-20116. doi: 10.1039/c8ra00679b. eCollection 2018 May 30.
10
Atorvastatin inhibits neuronal apoptosis via activating cAMP/PKA/p-CREB/BDNF pathway in hypoxic-ischemic neonatal rats.阿托伐他汀通过激活缺氧缺血新生大鼠的cAMP/PKA/p-CREB/BDNF通路抑制神经元凋亡。
FASEB J. 2022 Apr;36(4):e22263. doi: 10.1096/fj.202101654RR.