抑制蛋白酪氨酸磷酸酶通过增强糖尿病患者的Ang-1/Tie-2信号通路促进血管生成。

Experimental Diabetes Research Pub Date : 2012-01-01 Epub Date: 2012-02-12 DOI:10.1155/2012/836759
Jian-Xiong Chen, Qinhui Tuo, Duan-Fang Liao, Heng Zeng
{"title":"抑制蛋白酪氨酸磷酸酶通过增强糖尿病患者的Ang-1/Tie-2信号通路促进血管生成。","authors":"Jian-Xiong Chen,&nbsp;Qinhui Tuo,&nbsp;Duan-Fang Liao,&nbsp;Heng Zeng","doi":"10.1155/2012/836759","DOIUrl":null,"url":null,"abstract":"<p><p>Diabetes is associated with impairment of angiogenesis such as reduction of myocardial capillary formation. Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis. Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation. In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis. SHP-1 expression was significantly increased in diabetic db/db mouse hearts. Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC). Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation. Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation. Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC. Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis. Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.</p>","PeriodicalId":12109,"journal":{"name":"Experimental Diabetes Research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/836759","citationCount":"27","resultStr":"{\"title\":\"Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.\",\"authors\":\"Jian-Xiong Chen,&nbsp;Qinhui Tuo,&nbsp;Duan-Fang Liao,&nbsp;Heng Zeng\",\"doi\":\"10.1155/2012/836759\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Diabetes is associated with impairment of angiogenesis such as reduction of myocardial capillary formation. Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis. Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation. In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis. SHP-1 expression was significantly increased in diabetic db/db mouse hearts. Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC). Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation. Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation. Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC. Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis. Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.</p>\",\"PeriodicalId\":12109,\"journal\":{\"name\":\"Experimental Diabetes Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2012-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1155/2012/836759\",\"citationCount\":\"27\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Diabetes Research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1155/2012/836759\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2012/2/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Diabetes Research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/2012/836759","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2012/2/12 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 27

摘要

糖尿病与血管生成障碍有关,如心肌毛细血管形成减少。我们之前的研究表明,血管生成素-1 (ang1)/Tie-2信号通路的破坏有助于糖尿病相关的血管生成损伤。蛋白酪氨酸磷酸酶(Protein tyrosine phosphatase, PTP)通过抑制酪氨酸激酶磷酸化,在胰岛素信号调控中起关键作用。在本研究中,我们研究了蛋白酪氨酸磷酸酶-1 (SHP-1)在糖尿病相关的Ang-1/Tie-2血管生成信号和血管生成损伤中的作用。SHP-1在糖尿病小鼠心脏中表达显著升高。此外,SHP-1与Tie-2受体的结合和ang1的刺激导致SHP-1在小鼠心脏微血管内皮细胞(MHMEC)中与Tie-2分离。MHMEC暴露于高葡萄糖(HG, 30 mmol/L)会增加SHP-1/Tie-2的关联,同时Tie-2磷酸化显著降低。MHMEC暴露于HG也会减弱ang -1介导的SHP-1/Tie-2解离。敲低SHP-1可显著减弱hg诱导的MHMEC中caspase-3的激活和凋亡。PTP抑制剂可恢复ang -1诱导的Akt/eNOS磷酸化和血管生成。我们的数据暗示了SHP-1在糖尿病相关血管并发症中的关键作用,并且通过靶向SHP-1上调Ang-1/Tie-2信号传导应被视为治疗糖尿病相关血管生成损伤的新治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

摘要图片

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.

Diabetes is associated with impairment of angiogenesis such as reduction of myocardial capillary formation. Our previous studies demonstrate that disruption of Angiopoietin-1 (Ang-1)/Tie-2 signaling pathway contributes to the diabetes-associated impairment of angiogenesis. Protein tyrosine phosphatase (PTP) has a critical role in the regulation of insulin signal by inhibition of tyrosine kinase phosphorylation. In present study, we examined the role of protein tyrosine phosphatase-1 (SHP-1) in diabetes-associated impairment of Ang-1/Tie-2 angiogenic signaling and angiogenesis. SHP-1 expression was significantly increased in diabetic db/db mouse hearts. Furthermore, SHP-1 bond to Tie-2 receptor and stimulation with Ang-1 led to SHP-1 dissociation from Tie-2 in mouse heart microvascular endothelial cell (MHMEC). Exposure of MHMEC to high glucose (HG, 30 mmol/L) increased SHP-1/Tie-2 association accompanied by a significant reduction of Tie-2 phosphorylation. Exposure of MHMEC to HG also blunted Ang-1-mediated SHP-1/Tie-2 dissociation. Knockdown of SHP-1 significantly attenuated HG-induced caspase-3 activation and apoptosis in MHMEC. Treatment with PTP inhibitors restored Ang-1-induced Akt/eNOS phosphorylation and angiogenesis. Our data implicate a critical role of SHP-1 in diabetes-associated vascular complications, and that upregulation of Ang-1/Tie-2 signaling by targeting SHP-1 should be considered as a new therapeutic strategy for the treatment of diabetes-associated impairment of angiogenesis.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Experimental Diabetes Research
Experimental Diabetes Research 医学-内分泌学与代谢
自引率
0.00%
发文量
0
审稿时长
3-8 weeks
期刊最新文献
Nontraditional Therapy of Diabetes and Its Complications In Vitro Investigation and Evaluation of Novel Drug Based on Polyherbal Extract against Type 2 Diabetes Prevalence and Risk Factors Associated with Type 2 Diabetes in Elderly Patients Aged 45-80 Years at Kanungu District Erratum to “Circulating Levels of MicroRNA from Children with Newly Diagnosed Type 1 Diabetes and Healthy Controls: Evidence That miR-25 Associates to Residual Beta-Cell Function and Glycaemic Control during Disease Progression” A PEDF-derived peptide inhibits retinal neovascularization and blocks mobilization of bone marrow-derived endothelial progenitor cells.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1