Endogenous RNA sensing as a stimulant of skin regeneration

项目摘要 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。 糖尿病患者的皮肤常出现创面修复缺陷，出现压疮， 制动和静脉功能不全。如果伤口复发，它几乎只会复发在相同的位置， 最初的伤口，由于修复最初伤口的纤维化疤痕的脆弱性。伤口修复 通常导致纤维化疤痕组织区域。相比之下，皮肤再生完全重演 胚胎发生，完全恢复组织功能和附属器，如毛囊。通过理解这一点 在这个过程中，我们将能够促进再生，从而增强伤口修复。这样可以减少伤口 相关的住院及其相应的医疗费用，同时也提高了生活质量， 患者为了研究皮肤再生，本提案将使用创伤诱导毛发新生（WIHN） 比色法对于该测定，在小鼠上制造大的全厚度背部伤口，并允许通过收缩愈合 和再上皮化。在这些愈合的伤口的中心，数量不等的毛囊被完全吸收。 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。后 在创伤后，先天性免疫细胞，主要是嗜中性粒细胞和巨噬细胞，被募集到伤口床， 防止感染并促进修复。这项资助的目标是确定这些细胞在 再生过程中，重点是他们的贡献从头毛囊形成WIHN。在目标1中， 将研究小核RNA的表达和定位与浸润性肿瘤一致的假设， 免疫细胞。在目标2中，我们将研究浸润性免疫细胞是WIHN所需的假设。 在目标3中，我们将研究免疫细胞胞外陷阱促进毛囊生长的假设。 再生这些发现有可能导致纤维化治疗的重大进展。 疾病，影响皮肤、肝脏和肺等组织。本提案是一项指导培训补助金， 结合研究工作与必要的教学计划，为PI的未来过渡到一个独立的 位置

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.