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The basement membrane protein nidogen-1 supports platelet adhesion and activation

机译:基底膜蛋白Nidogen-1支持血小板粘附和活化

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摘要

The core structure of the extracellular basement membrane is made up of self-assembling networks of collagen and laminin which associate with each other through the bridging adapter proteins including the sulfated monomeric glycoprotein nidogen. While collagen and laminin are known to support platelet adhesion and activation via beta 1 integrins and glycoprotein (GP) VI, respectively, whether nidogen contributes to platelet activation and hemostasis is unknown. In this study, we demonstrate that recombinant human nidogen-1 supports platelet adhesion and stimulates platelet activation in a phospholipase-C gamma-2 (PLC gamma 2), Src and Syk kinase-dependent manner downstream. Platetet adhesion to nidogen-1 was inhibited by blocking the platelet receptors GPVI and beta 1 integrins. Platelet adhesion to nidogen-1 activated the I kappa B kinase (IKK) complex, while pharmacological inhibition of IKK blocked platelet spreading on nidogen. Taken together our results suggest that nidogen may play a redundant role in hemostasis by activating platelets downstream of GPVI.
机译:细胞外基膜的核心结构由胶原和层粘连蛋白的自组装网络组成,它们通过桥接适配器蛋白质相互结合,包括硫酸化单体糖蛋白巢蛋白。虽然已知胶原蛋白和层粘连蛋白分别通过β1整合素和糖蛋白(GP)VI支持血小板粘附和活化,但巢蛋白是否有助于血小板活化和止血尚不清楚。在这项研究中,我们证明重组人巢蛋白-1支持血小板粘附,并以磷脂酶-C-γ-2(PLC-γ2)、Src和Syk激酶依赖的方式在下游刺激血小板活化。通过阻断血小板受体GPVI和β1整合素,血小板与巢蛋白-1的粘附受到抑制。血小板与巢原-1的粘附激活了I-κB激酶(IKK)复合物,而对IKK的药理学抑制阻止了血小板在巢原上的扩散。综上所述,我们的研究结果表明,巢原可能通过激活GPVI下游的血小板在止血中发挥多余的作用。

著录项

  • 来源
    《Platelets》 |2021年第3期|共5页
  • 作者单位

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Knight Cardiovasc Inst Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Univ Strasbourg FMTS BPPS UMR S 1255 EFS Grand Est INSERM Strasbourg France;

    Univ Paris Diderot INSERM Sorbonne Paris Cite Lab Vasc Translat Sci Paris France;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

    Oregon Hlth &

    Sci Univ Dept Biomed Engn 3303 SW Bond Ave CH13B Portland OR 97239 USA;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 基础医学;
  • 关键词

    Extracellular matrix proteins; hemostasis; nidogen; platelet;

    机译:细胞外基质蛋白质;止血;氮素;血小板;

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