Cytokine Regulation of Wound Induced Skin Regeneration

描述（由申请人提供）：根据美国国立卫生研究院的数据，伤口护理每年花费约250亿美元。糖尿病、压疮、长时间制动和静脉功能不全的患者会出现皮肤伤口修复缺陷。当伤口复发时，它们几乎完全在与初始伤口相同的位置复发，这表明愈合过程的脆弱性和质量差。修复过程通常导致纤维化瘢痕组织的“补丁”-与皮肤再生相反，皮肤再生是胚胎发生的完全重演，组织功能和附件样毛囊完全替代。促进这种再生将改善伤口修复;因此，导致更少的截肢、降低的感染率和减少的住院治疗，同时相应地降低医疗成本和改善患者的生活质量。本提案将利用创伤诱导毛发再生（WIHN）试验来研究皮肤再生。小鼠中的大的全层皮肤切除物通过外周收缩和中心的上皮再形成而愈合。在愈合伤口（瘢痕）的中心区域，可变数量的毛囊完全再生，并且可以通过共聚焦扫描激光显微镜（CSLM）非侵入性地可视化。基因表达分析表明，与炎症和免疫反应相关的转录本在低再生（LR）和高再生（HR）样品之间差异最显著。该项目的总体假设是，不同的免疫介质促进和抑制皮肤再生。本项目将使用WIHN和CSLM来研究小鼠模型中的皮肤再生。在目标1中，我们将测试免疫细胞有助于皮肤再生的假设。在目标2中，我们将通过功能研究来检验IL-6促进WIHN的假设。这些发现可能导致影响皮肤、肝脏和肺等组织的纤维化疾病的治疗取得重大进展。这 该提案是一个指导培训补助金，结合研究工作与必要的PI的未来过渡到一个独立的位置教学计划。

DESCRIPTION (provided by applicant): Wound care costs approximately 25 billion dollars annually according to the National Institutes of Health. Defects in skin wound repair occur in patients with diabetes, pressure ulcers, prolonged immobilization and venous insufficiency. When wounds recur, they almost exclusively recur in the same location as the initial wound which indicates the fragility and poor quality of the healing process. The repair process usually results in a "patch" of fibrotic scar tissue-the opposite of skin regeneration, which is the full recapitulation of embryogenesis with complete replacement of tissue function and adnexa like hair follicles. Promotion of such regeneration will improve wound repair; thus, resulting in fewer amputations, decreased infection rates, and decreased hospitalizations with corresponding reductions in medical costs and improved quality of life for patients. This proposal will utilize te Wound Induced Hair Neogenesis (WIHN) assay to investigate skin regeneration. Large full-thickness skin excisions in mice heal by contraction on the periphery and re- epithelialization in the center. In the central area of the healed wound (scar), a variable number of hair follicles fuly regenerate and can be visualized non-invasively by confocal scanning laser microscopy (CSLM). Gene expression analysis demonstrated transcripts related to inflammation and immune responses were the most significantly different between low regeneration (LR) and high regeneration (HR) samples. The overall hypothesis underlying this project is that distinct immune mediators promote and inhibit skin regeneration. This project will use WIHN and CSLM to investigate skin regeneration in murine models. In Aim 1, we will test the hypothesis that immune cells contribute to skin regeneration. In Aim 2, we will test the hypothesis that IL-6 promotes WIHN through functional investigations. These findings can 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 PI's future transition to an independent position.