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Endogenous RNA sensing as a stimulant of skin regeneration

内源性 RNA 传感作为皮肤再生的刺激剂

基本信息

批准号：
9927483
负责人：
Eric Matthew Wier
金额：
$ 6.08万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-10 至 2021-02-27
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9927483
关键词：
Affect Antibodies Area Back Biological Assay Cells Chemicals Chromatin Chromatin Structure Cicatrix Coagulation Process Complement Coupled DNA Data Defect Diabetes Mellitus Disease Dorsal Double-Stranded RNA Embryonic Development Enzymes Epithelial Epithelium Event Excision Excretory function Extracellular Space Flow Cytometry Foundations Future Genetic Genetic Transcription Goals Grant Granulation Tissue Growth Factor Hair Hair follicle structure Hospitalization Immobilization Immune In Vitro Infection prevention Infiltration Inflammation Inflammatory Inflammatory Response Injections Injury Innate Immune System Internet Kinetics Knockout Mice Laser Scanning Confocal Microscopy Lead Ligands Liver Location Lung Medical Care Costs Mentors Mus Natural regeneration Neutrophil Infiltration Nuclear Outcome Patients Phagocytosis Phase Play Positioning Attribute Process Protein Inhibition Protein-arginine deiminase Quality of life RNA RNA Splicing Research Role Site Skeletal Muscle Skin Small Nuclear RNA Source Sterility Stimulus TLR3 gene Thick Time Tissues Training Tumor-infiltrating immune cells U1 small nuclear RNA United States National Institutes of Health Untranslated RNA Venous Insufficiency Work care costs chemical genetics cytokine decubitus ulcer extracellular healing human disease immune RNA improved keratinocyte mRNA Precursor macrophage neutrophil pathogen pathogenic virus receptor recruit repaired skin regeneration wound wound bed wound care wound closure wound healing

项目摘要

Project Summary According to the National Institutes of Health, wound care costs approximately 25 billion dollars annually. Wound repair defects often occur in the skin of patients with diabetes, pressure ulcers, prolonged immobilization, and venous insufficiency. If a wound recurs, it almost exclusively recurs in the same location as the initial wound, due to the fragility of the fibrotic scarring that repaired the initial wound. Wound repair typically results in a region of fibrotic scar tissue. Contrastingly, skin regeneration fully recapitulates embryogenesis, completely restoring tissue function and adnexa, such as hair follicles. By understanding this process, we will be able to promote regeneration, thereby augmenting wound repair. This would reduce wound related hospitalizations and their corresponding medical costs, while also improving the quality of life for patients. To investigate skin regeneration, this proposal will use the Wound Induced Hair Neogenesis (WIHN) assay. For the assay, large full-thickness dorsal wounds are made on mice, and allowed to heal by contraction and re-epithelialization. In the center of these healed wounds, a variable number of hair follicles are fully regenerated and can be visualized non-invasively by confocal scanning laser microscopy (CSLM). After wounding, innate immune cells, primarily neutrophils and macrophages, are recruited to the wound bed to prevent infection and facilitate repair. The goal of this grant is to define the role of these cells in the regeneration process, focusing on their contribution to de novo hair follicle formation during WIHN. In Aim 1 we will investigate the hypothesis that small nuclear RNA expression and localization coincides with infiltrating immune cells. In Aim 2 we will investigate the hypothesis that infiltrating immune cells are required for WIHN. In Aim 3 we will investigate the hypothesis that immune cell extracellular traps promote hair follicle regeneration. These findings have the potential to lead to significant advances in the treatment of fibrotic diseases, affecting tissues such as skin, liver, and lung. This proposal is a mentored training grant that combines research efforts with a didactic plan necessary for the future transition of the PI to an independent position.

项目总结