Deciphering the Piezo2-Merkel cell signaling mechanisms in itch

破译瘙痒中的 Piezo2-Merkel 细胞信号传导机制

基本信息

  • 批准号:
    10676917
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-08-01 至 2023-08-02
  • 项目状态:
    已结题

项目摘要

SUMMARY Itch is described as an unpleasant sensation that elicits the desire to scratch. Although acute scratching is the protective mechanism to remove irritants from the skin, chronic itch is debilitating. In addition, chronic itch is widespread and very difficult to treat because of a lack of understanding of the underlying mechanisms. Therefore, it is critical to gain a better understanding of the cellular and molecular basis of chronic itch toward the development of novel and effective therapies. Despite great progress in the past few decades in unraveling the role of membrane bound G-protein coupled receptors and ion channels, especially transient receptor potential (TRP) channels in the generation of itch sensation at the levels of primary sensory neurons and spinal cord, much remains unknown about how the cells and molecules in the skin contribute to the production and regulation of chronic itch other than the mediation of allergic itch by mast cells. Pilot studies showed that skin-specific knockout of Piezo2 severely reduced the spontaneous scratching in multiple mouse models of chronic itch. Moreover, the reduction of spontaneous itch in mice subjected to experimental dry skin is correlated with a loss of mechanically evoked C-fiber firing mediated by the TRPV1- positive C-mechanoreceptors. We thus hypothesized that Piezo2-Merkel cell signaling is required for the generation of spontaneous itch under chronic itch conditions by driving the TRPV1-positive C- mechanoreceptors under chronic itch conditions. In this grant proposal we will: 1) Use unique genetic approaches to investigate in vivo functions of the mechanosensitive Piezo2 channels and mechanosensory Merkel cells in mediating spontaneous itch three well-established mouse models of chronic itch; 2) Demonstrate that miswiring occurs between the Merkel cells and the pruriceptive C-type mechanoreceptor to promote spontaneous itch in chronic itch mice, thereby providing the cellular and molecular basis for chronic itch in multiple mouse models of chronic itch. Our findings will provide a major contribution to our general understanding of how Piezo2 channels and Merkel cells affect itch signaling in the skin, and undoubtedly lead to new therapeutic approaches for treating chronic itch.
总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Hongzhen Hu其他文献

Hongzhen Hu的其他文献

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{{ truncateString('Hongzhen Hu', 18)}}的其他基金

Genetic analysis of intrinsic sensory neuron function in the enteric neural circuits
肠神经回路中内在感觉神经元功能的遗传分析
  • 批准号:
    10568622
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Deciphering Ion Channel Mechanisms Underlying Mechanosensitivity in the Gut
破译肠道机械敏感性背后的离子通道机制
  • 批准号:
    10889525
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Deciphering the Piezo2-Merkel cell signaling mechanisms in itch
破译瘙痒中的 Piezo2-Merkel 细胞信号传导机制
  • 批准号:
    10890431
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Deciphering the Piezo2-Merkel cell signaling mechanisms in itch
破译瘙痒中的 Piezo2-Merkel 细胞信号传导机制
  • 批准号:
    10454374
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Deciphering the Piezo2-Merkel cell signaling mechanisms in itch
破译瘙痒中的 Piezo2-Merkel 细胞信号传导机制
  • 批准号:
    10225638
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
MECHANISMS OF TRPV4-MEDIATED NEUROPATHIC PAIN
TRPV4 介导的神经病理性疼痛的机制
  • 批准号:
    10204872
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
MECHANISMS OF TRPV4-MEDIATED NEUROPATHIC PAIN
TRPV4 介导的神经病理性疼痛的机制
  • 批准号:
    10443627
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
Deciphering Ion Channel Mechanisms Underlying Mechanosensitivity in the Gut
破译肠道机械敏感性背后的离子通道机制
  • 批准号:
    10454279
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
Deciphering Ion Channel Mechanisms Underlying Mechanosensitivity in the Gut
破译肠道机械敏感性背后的离子通道机制
  • 批准号:
    10116046
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:
TARGETING THE TRANSIENT RECEPTOR POTENTIAL CHANNELS TO IMPROVE BOWEL DYSFUNCTION
针对瞬时受体的潜在通道来改善肠功能障碍
  • 批准号:
    8962583
  • 财政年份:
    2015
  • 资助金额:
    --
  • 项目类别:

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