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Transduction of Mechanical Stimuli in Myelination and Peripheral Nerve Repair

髓鞘形成和周围神经修复中机械刺激的转导

基本信息

批准号：
10531613
负责人：
Yannick Poitelon
金额：
$ 38.65万
依托单位：
ALBANY MEDICAL COLLEGE
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：
2020-01-15 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10531613
关键词：
Ablation Affect Agonist Axon Cations Cell Differentiation process Cell physiology Cells Chemicals Clinical Treatment Cytoskeleton DNA-Binding Proteins Data Development Disease Economic Burden Elasticity Extracellular Matrix Fiber Funding Gene Expression Gene Expression Regulation Genes Genets Growth Health Impairment In Vitro Injury Ion Channel Knock-out Knockout Mice Mechanics Mediating Modeling Molecular Myelin Neuroglia Neuropathy Pathway interactions Peripheral Nerves Peripheral Nervous System Peripheral Nervous System Diseases Peripheral nerve injury Persons Physiologic pulse Piezo 1 ion channel Public Health Radial Regulation Research Role Schwann Cells Signal Transduction Stimulus Structure Symptoms Testing Therapeutic Therapeutic Effect Tissues Transducers Trauma Ultrasonic wave Variant axon injury design improved in vivo knock-down mechanical stimulus mechanotransduction mouse model myelination nervous system development new therapeutic target novel peripheral nerve regeneration peripheral nerve repair regeneration potential remyelination response sensor small hairpin RNA social transcription factor ultrasound

项目摘要

Mechanobiology is an emerging field which studies how physical forces and changes can contribute to cell differentiation, tissue formation and diseases. These forces are applied on cells through the local variations between neighbouring cells and the extracellular matrix. Notably, cell—cell and cell-extracellular matrix mechanical stimuli can stimulate electrochemical responses, the rearrangement of cytoskeletal structures and the regulation of gene expression. Schwann cells, the myelinating cells of the peripheral nervous system, are required for the function and health of the peripheral nervous system. Schwann cells also have a critical role in the regenerative potential of the peripheral nervous system, but very little is known about how Schwann cells sense axonal injury. We demonstrated that Schwann cells are exquisitely sensitive to alterations in the elasticity of the extracellular matrix; and that Schwann cell differentiation and myelination during the peripheral nervous system development depend on the transduction of mechanical stimuli by YAP and TAZ. Yet, it is unknown what are the signalling upstream and downstream YAP and TAZ in Schwann cells and if YAP and TAZ are also required for Schwann cell differentiation and remyelination after peripheral nerve injury. Here we will investigate if the transduction of mechanical stimuli in Schwann cells is critical to stimulate myelination and improve peripheral nerve regeneration. Our objectives are to determine if it is possible to manipulate Schwann cells mechanically to improve myelination, with therapeutic implications (Aim 3) and to discover new components of the mechanotransduction pathways upstream (Aim1) and downstream (Aim 2) of YAP and TAZ. Studying myelination through the mechanotransducers YAP and TAZ has potential to advance the field by identifying the therapeutic importance of Schwann cell and cellular mechanobiology and may reveal novel targets or mechanisms for myelin formation and peripheral nerve regeneration in neuropathies molecular.

机械生物学是一门研究物理力和物理变化如何影响细胞的新兴学科