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.
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 studies in this proposal address the mechanisms that regulate the skin regeneration process, focusing on the role of inflammation and the immune system.
|Nelson, Amanda M; Katseff, Adiya S; Ratliff, Tabetha S et al. (2016) Interleukin 6 and STAT3 regulate p63 isoform expression in keratinocytes during regeneration. Exp Dermatol 25:155-7|
|Nelson, Amanda M; Garza, Luis A (2015) Bad Hair Day: Testosterone and Wnts. J Invest Dermatol 135:2567-2569|
|Nelson, Amanda M; Reddy, Sashank K; Ratliff, Tabetha S et al. (2015) dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration. Cell Stem Cell 17:139-51|