Regulation of cutaneous axon regeneration by wound derived H2O2

伤口来源的 H2O2 对皮肤轴突再生的调节

• 批准号: 8465640
• 负责人: Sandra Rieger
• 金额: $ 32.32万
• 依托单位: MOUNT DESERT ISLAND BIOLOGICAL LAB
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8465640
• 关键词: Affect; Afferent Neurons; Aging; Axon; Candidate Disease Gene; Cell membrane; Cell physiology; Cells; Clinical; Comparative Biology; Cutaneous; Cysteine; Data; Detection; Diffuse; Diffusion; Disease; Disease model; Electron Microscopy; Environment; Extracellular Matrix; Failure; Fluorescence-Activated Cell Sorting; Future; Gene Expression Regulation; Genetic; Genetic Transcription; Goals; Health; Human; Hydrogen Peroxide; Image; Injury; Instruction; Investigation; Larva; Mediating; Messenger RNA; MicroRNAs; Modeling; Molecular; Natural regeneration; Neurons; Oxidases; Oxidation-Reduction; Paracrine Communication; Peripheral Nervous System Diseases; Phosphoric Monoester Hydrolases; Phosphotransferases; Property; Reactive Oxygen Species; Regulation; Research; Role; Sensory; Signal Pathway; Signal Transduction; Signaling Protein; Stimulus; Structure; Superoxides; Testing; Tissues; Trauma; Work; Wound Healing; Zebrafish; axon growth; axon regeneration; cell injury; chemical property; comparative; crosslink; deep sequencing; dityrosine; functional genomics; in vivo; innovation; insight; keratinocyte; mRNA Expression; oxidation; repaired; response to injury; retrograde transport; somatosensory; therapy development; tissue repair; tool; transcription factor; water channel; wound

PROJECT SUMMARY (See instructions): The ability to regenerate cutaneous sensory axons in response to injury is crucial for restoring tissue function. Despite its importance and many research efforts in the past, the mechanisms for cutaneous axon regeneration following injury have remained elusive. We have previously discovered that the small reactive oxygen species hydrogen peroxide (H2O2) is a key regulatory molecule for stimulating cutaneous axon growth. Historically, H2O2 has been seen as a cell-damaging molecule, when present at high concentrations in cells. Recent work however, demonstrates that low, non-toxic concentrations of H2O2 are important for regulation of many cellular functions. This is achieved by the oxidation of redox-sensitive cysteine residues in signaling proteins, most notably of kinases, phosphatases, and transcription factors, which alters their structure and function. As the research field of H2O2 signaling is relatively new, insight into its signaling properties during tissue repair is only beginning to emerge. The significance of this proposal is that it will elucidate mechanisms utilized by injury-induced H2O2 that stimulate cutaneous axon regeneration. The insight gained from this research will aid in the development of treatments for damaged axons due to disease or trauma. Our approach is to combine in vivo imaging and parallel deep sequencing of miRNAs and mRNAs to analyze H2O2 responsive genetic networks in somatosensory neurons that are essential for stimulating axon regeneration.

项目摘要（参见说明）： 响应损伤而再生皮肤感觉轴突的能力对于恢复组织功能至关重要。尽管其重要性以及过去的许多研究工作，损伤后皮肤轴突再生的机制仍然难以捉摸。我们之前发现，小活性氧过氧化氢（H2O2）是刺激皮肤轴突生长的关键调节分子。从历史上看，H2O2 在高浓度存在时被视为一种细胞损伤分子 在细胞中。然而，最近的研究表明，低浓度、无毒的 H2O2 对于许多细胞功能的调节非常重要。这是通过信号蛋白（尤其是激酶、磷酸酶和转录因子）中氧化还原敏感的半胱氨酸残基的氧化来实现的，这会改变它们的结构和功能。由于 H2O2 信号传导的研究领域相对较新，因此对其在组织修复过程中的信号传导特性的深入了解才刚刚开始出现。该提案的意义在于，它将阐明损伤诱导的 H2O2 刺激皮肤轴突再生的机制。从这项研究中获得的见解将有助于开发针对因疾病或创伤而受损的轴突的治疗方法。我们的方法是将体内成像与 miRNA 和 mRNA 的并行深度测序相结合，分析体感神经元中的 H2O2 响应遗传网络，这对于刺激轴突再生至关重要。