• 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

内皮酪氨酸磷酸酶 SHP-1 在 TNFα 诱导的体内炎症中的血管止血中起着重要作用。

The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular haemostasis in TNFα -induced inflammation in vivo.

机构信息

Medizinische Klinik und Poliklinik IV, Innenstadt, Ludwig Maximilians Universität München, Ziemssenstr 1, 80336 Munich, Germany.

出版信息

Mediators Inflamm. 2013;2013:279781. doi: 10.1155/2013/279781. Epub 2013 May 9.

DOI:10.1155/2013/279781
PMID:23766558
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3665258/
Abstract

INTRODUCTION

Inflammation and endothelium-derived superoxides are important pathomechanisms in atherothrombotic diseases. We could previously show that the tyrosine phosphatase SHP-1 acts as a negative regulator in endothelial superoxide production. In this study we investigated the influence of SHP-1 on platelet-endothelium interaction and arterial thrombosis in TNFα -induced endothelial inflammation in vivo.

METHODS

Arteriolar thrombosis and platelet rolling in vivo were investigated in C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model.

RESULTS

Inhibition of SHP-1 by the specific pharmacological inhibitor sodium stibogluconate did not significantly enhance platelet-endothelium interaction in vivo under physiological conditions but led to an augmented fraction of rolling platelets in TNFα -induced systemic inflammation. Accordingly, ferric-chloride-induced arteriolar thrombus formation, which was already increased by SHP-1 inhibition, was further enhanced in the setting of TNFα -induced inflammation. Platelet aggregation in vitro as well as ex vivo was not influenced by SHP-1-inhibition. In cultured endothelial cells, sodium stibogluconate increased TNFα -induced surface expression of p-selectin and von Willebrand factor. Additionally, TNFα increased SHP-1 activity and protein expression.

CONCLUSIONS

The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular hemostasis in vivo, which is crucial in TNF α -induced endothelial inflammation where it may serve as an autoinhibitory molecule to prevent excess inflammatory response and thrombus formation.

摘要

简介

炎症和内皮衍生的超氧化物是动脉血栓形成疾病的重要发病机制。我们之前已经证明，酪氨酸磷酸酶 SHP-1 作为内皮细胞中超氧化物产生的负调节剂起作用。在这项研究中，我们研究了 SHP-1 对 TNFα 诱导的内皮炎症体内血小板-内皮相互作用和动脉血栓形成的影响。

方法

在背部皮肤囊微循环模型中使用活体显微镜研究 C57BL/6 小鼠体内的小动脉血栓形成和血小板滚动。

结果

特异性的丝氨酸/苏氨酸磷酸酶 SHP-1 抑制剂单钠葡庚糖酸盐在生理条件下并未显著增强体内血小板-内皮相互作用，但在 TNFα 诱导的全身炎症中导致滚动血小板的比例增加。相应地，铁氯酸盐诱导的小动脉血栓形成已经被 SHP-1 抑制增强，在 TNFα 诱导的炎症中进一步增强。体外和体内的血小板聚集不受 SHP-1 抑制的影响。在培养的内皮细胞中，单钠葡庚糖酸盐增加了 TNFα 诱导的 p-选择素和血管性血友病因子的表面表达。此外，TNFα 增加了 SHP-1 的活性和蛋白表达。

结论

内皮细胞中的酪氨酸磷酸酶 SHP-1 在体内血管止血中起重要作用，在 TNFα 诱导的内皮炎症中至关重要，它可能作为一种自身抑制分子，防止过度的炎症反应和血栓形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/1fd338951207/MI2013-279781.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/07167f425882/MI2013-279781.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/6230343ea5a4/MI2013-279781.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/b873f732c075/MI2013-279781.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/1b8f86eb8c68/MI2013-279781.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/1fd338951207/MI2013-279781.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/07167f425882/MI2013-279781.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/6230343ea5a4/MI2013-279781.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/b873f732c075/MI2013-279781.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/1b8f86eb8c68/MI2013-279781.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a973/3665258/1fd338951207/MI2013-279781.005.jpg

相似文献

1
The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular haemostasis in TNFα -induced inflammation in vivo.内皮酪氨酸磷酸酶 SHP-1 在 TNFα 诱导的体内炎症中的血管止血中起着重要作用。
Mediators Inflamm. 2013;2013:279781. doi: 10.1155/2013/279781. Epub 2013 May 9.
2
Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of TNF-alpha receptor subtype 1 and require TNF-alpha receptor subtype 2.肿瘤坏死因子α在体内的促血栓形成作用因缺乏肿瘤坏死因子α受体亚型1而增强，且需要肿瘤坏死因子α受体亚型2。
Arthritis Res Ther. 2012 Oct 18;14(5):R225. doi: 10.1186/ar4064.
3
Sodium stibogluconate is a potent inhibitor of protein tyrosine phosphatases and augments cytokine responses in hemopoietic cell lines.葡萄糖酸锑钠是一种有效的蛋白酪氨酸磷酸酶抑制剂，可增强造血细胞系中的细胞因子反应。
J Immunol. 2001 Sep 15;167(6):3391-7. doi: 10.4049/jimmunol.167.6.3391.
4
Effects of SOV-induced phosphatase inhibition and expression of protein tyrosine phosphatases in rat corneal endothelial cells.SOV诱导的磷酸酶抑制作用及蛋白酪氨酸磷酸酶在大鼠角膜内皮细胞中的表达影响
Exp Eye Res. 2005 Nov;81(5):570-80. doi: 10.1016/j.exer.2005.03.015. Epub 2005 Jun 13.
5
A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein-dependent signaling.一个新鉴定的突触后密度蛋白 95（spinophilin）和酪氨酸磷酸酶 SHP-1 复合物通过调节 G 蛋白依赖性信号转导来调节血小板激活。
Blood. 2012 Feb 23;119(8):1935-45. doi: 10.1182/blood-2011-10-387910. Epub 2011 Dec 30.
6
The tyrosine phosphatase, SHP-1, is a negative regulator of endothelial superoxide formation.酪氨酸磷酸酶SHP-1是内皮细胞超氧化物生成的负调节因子。
J Am Coll Cardiol. 2005 May 17;45(10):1700-6. doi: 10.1016/j.jacc.2005.02.039.
7
Real-time imaging of heterotypic platelet-neutrophil interactions on the activated endothelium during vascular inflammation and thrombus Formation in live mice.实时成像观察活体内小鼠血管炎症和血栓形成过程中，激活的内皮细胞上异型血小板与中性粒细胞的相互作用。
J Vis Exp. 2013 Apr 2(74):50329. doi: 10.3791/50329.
8
Prothrombotic effects of diclofenac on arteriolar platelet activation and thrombosis in vivo.双氯芬酸对活体小动脉血小板激活和血栓形成的促血栓形成作用。
J Thromb Haemost. 2009 Oct;7(10):1727-35. doi: 10.1111/j.1538-7836.2009.03582.x. Epub 2009 Aug 19.
9
Advanced glycation end product Nε-carboxymethyllysine induces endothelial cell injury: the involvement of SHP-1-regulated VEGFR-2 dephosphorylation.晚期糖基化终产物 Nε-羧甲基赖氨酸诱导内皮细胞损伤：涉及 SHP-1 调节的 VEGFR-2 去磷酸化。
J Pathol. 2013 Jun;230(2):215-27. doi: 10.1002/path.4045. Epub 2013 Mar 12.
10
SHP-1 phosphatase activity counteracts increased T cell receptor affinity.SHP-1 磷酸酶活性可拮抗 T 细胞受体亲和力的增加。
J Clin Invest. 2013 Mar;123(3):1044-56. doi: 10.1172/JCI65325. Epub 2013 Feb 8.

引用本文的文献

1
SHP1 and its downstream p38/SP1/PI3K/YAP/Notch-1 signaling in trophoblast cells suppressed the progression of Preeclampsia via inhibiting proliferation of SMCs.滋养层细胞中的SHP1及其下游的p38/SP1/PI3K/YAP/Notch-1信号通路通过抑制平滑肌细胞增殖抑制了子痫前期的进展。
Sci Rep. 2025 May 9;15(1):16205. doi: 10.1038/s41598-025-00164-6.
2
Endothelial PTP4A1 mitigates vascular inflammation via USF1/A20 axis-mediated NF-κB inactivation.内皮 PTP4A1 通过 USF1/A20 轴介导的 NF-κB 失活减轻血管炎症。
Cardiovasc Res. 2023 May 22;119(5):1265-1278. doi: 10.1093/cvr/cvac193.
3
Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.

本文引用的文献

1
Hypoxia-inducible plasmid expressing both miSHP-1 and HO-1 for the treatment of ischemic disease.表达 miSHP-1 和 HO-1 的缺氧诱导质粒用于治疗缺血性疾病。
J Control Release. 2013 Jan 10;165(1):22-8. doi: 10.1016/j.jconrel.2012.10.014. Epub 2012 Oct 26.
2
Prothrombotic effects of tumor necrosis factor alpha in vivo are amplified by the absence of TNF-alpha receptor subtype 1 and require TNF-alpha receptor subtype 2.肿瘤坏死因子α在体内的促血栓形成作用因缺乏肿瘤坏死因子α受体亚型1而增强，且需要肿瘤坏死因子α受体亚型2。
Arthritis Res Ther. 2012 Oct 18;14(5):R225. doi: 10.1186/ar4064.
3
Flavonoids: antioxidants against atherosclerosis.
靶向蛋白磷酸酶治疗炎症相关疾病：从信号转导到治疗。
Signal Transduct Target Ther. 2022 Jun 4;7(1):177. doi: 10.1038/s41392-022-01038-3.
4
SHP-1 suppresses endotoxin-induced uveitis by inhibiting the TAK1/JNK pathway.SHP-1 通过抑制 TAK1/JNK 通路抑制内毒素诱导的葡萄膜炎。
J Cell Mol Med. 2021 Jan;25(1):147-160. doi: 10.1111/jcmm.15888. Epub 2020 Nov 18.
5
Vitamin D3-VDR-PTPN6 axis mediated autophagy contributes to the inhibition of macrophage foam cell formation.维生素 D3-VDR-PTPN6 轴介导的自噬有助于抑制巨噬细胞泡沫细胞形成。
Autophagy. 2021 Sep;17(9):2273-2289. doi: 10.1080/15548627.2020.1822088. Epub 2020 Sep 24.
6
Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell-platelet-monocyte interaction.CD40 和 ADAMTS13 在血管性血友病因子介导的血管内皮细胞-血小板-单核细胞相互作用中的作用。
Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5556-E5565. doi: 10.1073/pnas.1801366115. Epub 2018 May 23.
7
The tyrosine phosphatase SHP-1 regulates hypoxia inducible factor-1α (HIF-1α) protein levels in endothelial cells under hypoxia.酪氨酸磷酸酶SHP-1在缺氧条件下调节内皮细胞中缺氧诱导因子-1α（HIF-1α）的蛋白水平。
PLoS One. 2015 Mar 23;10(3):e0121113. doi: 10.1371/journal.pone.0121113. eCollection 2015.
8
Inhibition of protein tyrosine phosphatases enhances cerebral collateral growth in rats.抑制蛋白酪氨酸磷酸酶可促进大鼠脑侧支循环生长。
J Mol Med (Berl). 2014 Sep;92(9):983-94. doi: 10.1007/s00109-014-1164-z. Epub 2014 May 27.
9
A diaCEST MRI approach for monitoring liposomal accumulation in tumors.一种用于监测肿瘤中脂质体积累的 diaCEST MRI 方法。
J Control Release. 2014 Apr 28;180:51-9. doi: 10.1016/j.jconrel.2014.02.005. Epub 2014 Feb 15.
类黄酮：对抗动脉粥样硬化的抗氧化剂。
Nutrients. 2010 Aug;2(8):889-902. doi: 10.3390/nu2080889. Epub 2010 Aug 12.
4
ARNO regulates VEGF-dependent tissue responses by stabilizing endothelial VEGFR-2 surface expression.ARNO 通过稳定内皮 VEGFR-2 表面表达来调节 VEGF 依赖性组织反应。
Cardiovasc Res. 2012 Jan 1;93(1):111-9. doi: 10.1093/cvr/cvr265. Epub 2011 Oct 13.
5
Role of tumor necrosis factor-α in the extraintestinal thrombosis associated with colonic inflammation.肿瘤坏死因子-α在与结肠炎症相关的肠道外血栓形成中的作用。
Inflamm Bowel Dis. 2011 Nov;17(11):2217-23. doi: 10.1002/ibd.21593. Epub 2010 Dec 16.
6
Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease.Lyn 和 PLC-beta3 依赖性调节 SHP-1 磷酸化控制 Stat5 活性和髓系白血病样疾病。
Blood. 2010 Dec 23;116(26):6003-13. doi: 10.1182/blood-2010-05-283937. Epub 2010 Sep 21.
7
Suppression of DNA-PKcs enhances FGF-2 dependent human endothelial cell proliferation via negative regulation of Akt.DNA依赖蛋白激酶催化亚基（DNA-PKcs）的抑制通过对Akt的负调控增强了成纤维细胞生长因子-2（FGF-2）依赖的人内皮细胞增殖。
Cell Signal. 2010 Jan;22(1):88-96. doi: 10.1016/j.cellsig.2009.09.015. Epub 2009 Sep 23.
8
Role of TNF-alpha in vascular dysfunction.肿瘤坏死因子-α在血管功能障碍中的作用。
Clin Sci (Lond). 2009 Feb;116(3):219-30. doi: 10.1042/CS20080196.
9
TNF-alpha employs a protein-tyrosine phosphatase to inhibit activation of hepatocyte growth factor receptor and hepatocyte growth factor-induced endothelial cell proliferation.肿瘤坏死因子-α利用一种蛋白酪氨酸磷酸酶来抑制肝细胞生长因子受体的激活以及肝细胞生长因子诱导的内皮细胞增殖。
Mol Cell Biochem. 2009 Feb;322(1-2):113-7. doi: 10.1007/s11010-008-9946-7. Epub 2008 Nov 12.
10
Role of inflammation in atherosclerosis associated with rheumatoid arthritis.炎症在类风湿关节炎相关动脉粥样硬化中的作用。
Am J Med. 2008 Oct;121(10 Suppl 1):S21-31. doi: 10.1016/j.amjmed.2008.06.014.