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Adipocyte lipolysis regulates skin repair

脂肪细胞脂肪分解调节皮肤修复

基本信息

批准号：
10408672
负责人：
Valerie Horsley
金额：
$ 43.5万
依托单位：
YALE 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：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10408672
关键词：
Acute Adipocytes Adipose tissue Affect Age Aging Bacterial Infections Binding Biological Assay Cell physiology Cells Cicatrix Collaborations Data Dermal Dermis Diabetes Mellitus Diabetic mouse Diagnostic Fatty Acids Fibrosis Financial Hardship Generations Genetic Glucocorticoid Receptor Glucocorticoids Goals Growth Hair Healthcare Systems Human Infectious Skin Diseases Inflammation Inflammatory Injury Laboratories Lead Lipids Lipolysis Maintenance Mediating Metabolism Mus Nuclear Receptors Obesity Pathway interactions Patients Population Process Production Role Signal Transduction Skin Skin injury Skin repair Skin wound healing Testing Therapeutic Tissue Engineering Tissue Model Tissues Work adipocyte biology aged base cell type chronic wound cytokine diabetic diabetic patient effective therapy experimental study healing human disease improved injured lipidomics macrophage monocyte mouse model novel obese patients personalized medicine recruit regenerative therapy response skin disorder skin regeneration skin wound statistics therapeutic target therapy development tissue repair wound wound bed wound healing

项目摘要

Project Summary My laboratory recently uncovered an unexpected and intriguing role for mature adipocytes during skin wound healing: control of inflammation after injury. In particular, we identified that mature adipocytes undergo lipolysis to release of lipids into wound beds to initiate inflammation. Our findings are important for several reasons. First, adipocytes have been shown to improve wound healing and scarring yet how mature adipocytes function in this process is unclear. Second, the release of lipids from adipocytes, or lipolysis, has been shown to modulate inflammation in traditional depots, yet whether skin adipocytes regulate the essential inflammatory processes following skin injury is not known. Furthermore, adipocytes and their derivatives (fatty acids and/or cytokines) are a tractable cell type to create a personalized therapy to promote healing in patients with chronic wounds. Finally, glucocorticoids are known to influence adipocyte biology and also to inhibit wound healing, but whether the effect of glucocorticoids on wound healing is mediated through adipocytes is not known. Through three focused and complementary Specific Aims, the work proposed in this application will take advantage of multiple genetic mouse models that allow specific depletion of adipocytes, adipocyte lipolysis, lipidomics, lipid tracking, bioengineered tissue models, and a novel bioanalytical assay platform to define the function adipocyte-derived lipids during skin injury and how these are altered with glucocorticoids, age, diabetes and obesity. We will (1) identify the role of adipocyte derived lipids during inflammation during skin wound healing, (2) determine whether glucocorticoids influence wound healing through depletion of lipids from mature, dermal adipocytes, (3) define whether adipocyte fatty acids can modulate wound healing in aged and diabetic mice or are altered in human skin. These studies will identify specific pro-healing cell populations and molecules that can be utilized to promote healing in human patients with defective wound healing or other skin disorders.

项目总结