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首页> 外文期刊>Neuron >miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus
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miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus

机译：miRNA-711结合并激活TRPA1以引起急性和慢性瘙痒症

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摘要

Increasing evidence suggests that extracellular miRNAs may serve as biomarkers of diseases, but the physiological relevance of extracellular miRNA is unclear. We find that intradermal cheek injection of miR-711 induces TRPA1-depedent itch (scratching) without pain (wiping) in naive mice. Extracellular perfusion of miR-711 induces TRPA1 currents in bothTrpa1-expressing heterologous cells and native sensory neurons through the core sequence GGGACCC. Computer simulations reveal that the core sequence binds several residues at the extracellular S5-S6 loop of TRPA1, which are critical for TRPA1 activation by miR-711 but not allyl isothiocyanate. Intradermal inoculation of human Myla cells induces lymphoma and chronic itch in immune-deficient mice, associated with increased serum levels of miR-711, secreted from cancer cells. Lymphoma-induced chronic itch is suppressed by miR-711 inhibitor and a blocking peptide that disrupts the miR-711/TRPA1 interaction. Our findings demonstrated an unconventional physiological role of extracellular naked miRNAs as itch mediators and ion channel modulators.
机译：越来越多的证据表明，细胞外miRNA可以作为疾病的生物标志物，但细胞外miRNA的生理相关性尚不清楚。我们发现皮内脸颊注射miR-711诱导TRPA1-DEPEDENT ITCH（刮擦），而不会在幼稚小鼠中疼痛（擦拭）。 miR-711的细胞外灌注在辛曲线序列GGGACCC通过核心序列诱导TRPA1的异源细胞和天然感官神经元。计算机模拟显示核心序列在TRPA1的细胞外S5-S6环中结合几个残基，这对于MIR-711的TRPA1活化至关重要，但不是烯丙基异硫氰酸酯。人myla细胞的皮内接种在免疫缺陷小鼠中诱导淋巴瘤和慢性瘙痒，与癌细胞分泌的miR-711的血清水平增加相关。淋巴瘤诱导的慢性瘙痒受MiR-711抑制剂和破坏miR-711 / TRPA1相互作用的阻断肽抑制。我们的研究结果表明，细胞外裸体miRNA作为瘙痒介导和离子通道调节剂的非常规生理作用。

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  • 来源
    《Neuron》 |2018年第3期|共15页
  • 作者

    Qingjian Han; Di Liu; Marino Convertino; Zilong Wang; Changyu Jiang; Yong Ho Kim; Xin Luo; Xin Zhang; Andrea Nackley; Nikolay V. Dokholyan; Ru-Rong Ji;

  • 作者单位

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

    Department of Biochemistry and Biophysics University of North Carolina;

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

    Department of Biochemistry and Biophysics University of North Carolina;

    Center for Translational Pain Medicine Department of Anesthesiology Duke University Medical Center;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

    Dorsal root ganglion (DRG); miRNAs; itch; lymphoma; mice; pain; pruritus; scratching; Toll-like receptor 7 (TLR7); transient receptor potential ankyrin 1 (TRPA1);

    机译：背根神经节（DRG）;miRNA;瘙痒;淋巴瘤;小鼠;疼痛;瘙痒;划伤;刮擦受体7（TLR7）;瞬态受体潜在的Ankyrin 1（TRPA1）;

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