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首页> 外文期刊>Arteriosclerosis, thrombosis, and vascular biology >Cell-Specific Effects of GATA (GATA Zinc Finger Transcription Factor Family)-6 in Vascular Smooth Muscle and Endothelial Cells on Vascular Injury Neointimal Formation
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Cell-Specific Effects of GATA (GATA Zinc Finger Transcription Factor Family)-6 in Vascular Smooth Muscle and Endothelial Cells on Vascular Injury Neointimal Formation

机译:GATA(GATA锌指转录因子家族)-6在血管平滑肌和内皮细胞上的细胞特异性效应新内膜细胞

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摘要

Objective-Transcription factor GATA (GATA zinc finger transcription factor family)-6 is highly expressed in vessels and rapidly downregulated in balloon-injured carotid arteries and viral delivery of GATA-6 to the vessels limited the neointimal formation, however, little is known about its cell-specific regulation of in vivo vascular smooth muscle cell (VSMC) phenotypic state contributing to neointimal formation. This study aims to determine the role of vascular cellspecific GATA-6 in ligation-or injury-induced neointimal hyperplasia in vivo. Approach and Results-Endothelial cell and VSMC-specific GATA-6 deletion mice are generated, and the results indicate that endothelial cell-specific GATA-6 deletion mice exhibit significant decrease of VSMC proliferation and attenuation of neointimal formation after artery ligation and injury compared with the wild-type littermate control mice. PDGF (plateletderived growth factor)-B is identified as a direct target gene, and endothelial cell-GATA-6-PDGF-B pathway regulates VSMC proliferation and migration in a paracrine manner which controls the neointimal formation. In contrast, VSMCspecific GATA-6 deletion promotes injury-induced VSMC transformation from contractile to proliferative synthetic phenotype leading to increased neointimal formation. CCN (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed family)-5 is identified as a novel target gene, and VSMC-specific CCN-5 overexpression in mice reverses the VSMC-GATA-6 deletion-mediated increased cell proliferation and migration and finally attenuates the neointimal formation. Conclusions-This study gives us a direct in vivo evidence of GATA-6 cell lineage-specific regulation of PDGF-B and CCN-5 on VSMC phenotypic state, proliferation and migration contributing to neointimal formation, which advances our understanding of in vivo neointimal hyperplasia, meanwhile also provides opportunities for future therapeutic interventions.
机译:目的转录因子GATA(GATA锌指转录因子家族)-6在血管中高度表达,并且在气球伤害颈动脉和GATA-6的病毒递送到血管的病毒递送限制了新的形成,但是,关于新的形成很少其细胞特异性调节体内血管平滑肌细胞(VSMC)表型患者有助于内部形成。本研究旨在确定血管细胞特异性GATA-6在所述体内结扎或损伤诱导的新内膜增生中的作用。产生方法和结果 - 内皮细胞和VSMC特异性GATA-6缺失小鼠,结果表明,内皮细胞特异性GATA-6缺失小鼠表现出VSMC增殖的显着降低和动脉结扎和损伤后内膜形成的衰减。与野生型凋落物对小鼠。 PDGF(血小板的生长因子)-B被鉴定为直接靶基因,内皮细胞 - GATA-6-PDGF-B途径调节VSMC的增殖和迁移以帕拉卡碱的方式,其控制新内膜地层。相比之下,VSMC特异性GATA-6缺失促进损伤诱导的VSMC转化从收缩到增殖合成表型导致新内膜形成增加。 CCN(富含半胱氨酸的61 /结缔组织生长因子/肾素母细胞瘤过表达家族)-5被鉴定为新的靶基因,小鼠中的VSMC特异性CCN-5过表达逆转VSMC-GATA-6缺失介导的细胞增殖和迁移并最终衰减新内部形成。结论 - 本研究向我们提供了一种直接的体内证据,即PDGF-B和CCN-5对VSMC表型状态,增殖和迁移有助于内膜形成的促进,这使得我们对体内内膜增生的理解进展同时,同时也为未来的治疗干预提供了机会。

著录项

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  • 作者单位

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

    Tongji Univ Shanghai East Hosp Sch Med Dept Cardiol Shanghai Peoples R China;

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

    Chinese Univ Hong Kong Dept Med &

    Therapeut Hong Kong Peoples R China;

    Taipei Med Univ Wan Fang Hosp Dept Internal Med Div Cardiol Taipei Taiwan;

    Tongji Univ Shanghai East Hosp Sch Med Dept Cardiol Shanghai Peoples R China;

    Tongji Univ Shanghai East Hosp Sch Med Dept Cardiol Shanghai Peoples R China;

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

    Tianjin Med Univ Sch Basic Med Sci Dept Pharmacol Tianjin Peoples R China;

    Columbia Univ Dept Med Cardiol Div New York NY USA;

    Univ Penn Penn Inst Regenerat Med Penn Cardiovasc Inst Dept Cell &

    Dev Biol Dept Med;

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

    Tongji Univ Shanghai East Hosp Res Ctr Translat Med Key Lab Arrhythmias Minist Educ China Sch;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 心脏、血管(循环系)疾病;
  • 关键词

    carotid arteries; cell lineage; endothelial cells; hyperplasia; transcription factors;

    机译:颈动脉;细胞谱系;内皮细胞;增生;转录因子;

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