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: 8856274
• 负责人: Sandra Rieger
• 金额: $ 37.45万
• 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 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8856274
• 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; Injury; Instruction; Investigation; Larva; Mediating; Messenger RNA; MicroRNAs; Modeling; Molecular; Natural regeneration; Nerve 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 injury; axon regeneration; cell injury; chemical property; comparative; crosslink; deep sequencing; dityrosine; functional genomics; in vivo; in vivo imaging; 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.

项目概述（见说明）：