Extrinsic Regulation of Epidermal Homeostatasis

表皮稳态的外在调节

• 批准号: 8460545
• 负责人: Valerie Horsley
• 金额: $ 35.57万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460545
• 关键词: Address; Adipocytes; Adipose tissue; Adult; Affect; Alopecia; Behavior; Behavior Control; Biological Assay; Biology; Blood Vessels; Bone Marrow; Cell Communication; Cell Lineage; Cells; Chronic; Data; Defect; Dermal; Dermis; Development; Disease; Endocrine; Environment; Epidermis; Epithelial; Epithelial Cells; Epithelium; Fibroblasts; Future; Gene Mutation; Genetic; Goals; Growth; Hair; Hair follicle structure; Hair shaft structure; Homeostasis; Immune; Infection; Kinetics; Lead; Ligands; Lipids; Maintenance; Mammals; Mammary gland; Mediating; Modeling; Molecular; Mus; Mutation; Natural regeneration; Paracrine Communication; Patients; Pattern; Phenotype; Physiology; Platelet-Derived Growth Factor; Platelet-Derived Growth Factor Receptor; Play; Process; Proliferating; Regulation; Research; Role; Signal Pathway; Signaling Molecule; Skeletal Muscle; Skeletal bone; Skin; Skin Tissue; Stem cells; Testing; Time; Tissues; Work; Wound Healing; animal tissue; appendage; base; cell behavior; cell type; cytokine; human disease; improved; in vitro Assay; in vivo; injured; lipid biosynthesis; mouse model; precursor cell; progenitor; regenerative; regenerative therapy; repaired; response; self-renewal

DESCRIPTION (provided by applicant): The long-term goal of this project is to better understand the tissue microenvironment that controls the activity and behavior of epithelial stem cells. Epithelial stem cells are responsible for the maintenance and regeneration of self-renewing tissues such as epidermis, hair follicle, and mammary gland. We have begun analyzing the biology and function of subdermal adipocytes during skin tissue homeostasis. In mammals, depots of white adipose tissue store energy through lipid accumulation and can serve as paracrine signaling tissues. In the skin, subdermal adipocytes compose a unique adipose tissue depot that underlies the dermal fibroblasts and surrounds the hair follicle during hair growth. Data suggests that adipocytes may regulate hair follicle cycling and wounding, but the role of subdermal adipocytes in the skin is not known. Our preliminary data shows that subdermal adipocytes are essential for hair follicle cycling and wound healing and generate a dynamic microenvironment in the skin. We hypothesize that the interplay between skin cells and subdermal adipocytes is crucial for the regulation of epidermal homeostasis. To address this hypothesis, we will: 1. characterize whether subdermal adipocytes are important for maintaining the hair follicle stem cell phenotype by a. analyzing mice with genetic or pharmacologically induced defects in adipogenesis, resulting in defects in subdermal adipocytes and b. defining adipogenesis during the hair cycle. 2. determine if subdermal adipocytes play a role in epidermal wound healing by a. defining the wound healing response in mice with defects in subdermal adipocytes and b. defining the cellular mechanisms that lead to adipocyte regeneration during wound healing. 3. Define the molecular mechanisms by which subdermal adipocytes regulate skin homeostasis using in vitro assays with adipocytes to address the role of signaling molecule expression by these adipocytes in the skin. Patients with alopecia, hair shaft disorders, or chronic wounds could potentially benefit from this research.

描述（由申请人提供）： 该项目的长期目标是更好地了解控制上皮干细胞活性和行为的组织微环境。上皮干细胞负责维持和再生自我更新的组织，如表皮、毛囊和乳腺。我们已经开始分析皮下脂肪细胞在皮肤组织稳态中的生物学和功能。在哺乳动物中，白色脂肪组织通过脂质积累储存能量，并可作为旁分泌信号组织。在皮肤中，皮下脂肪细胞构成独特的脂肪组织库，其位于真皮成纤维细胞之下并在毛发生长期间包围毛囊。数据表明，脂肪细胞可以调节毛囊周期和创伤，但皮下脂肪细胞在皮肤中的作用尚不清楚。我们的初步数据表明，皮下脂肪细胞对毛囊循环和伤口愈合至关重要，并在皮肤中产生动态微环境。我们推测皮肤细胞和皮下脂肪细胞之间的相互作用对表皮稳态的调节至关重要。为了解决这个问题，我们将：1。通过a.表征皮下脂肪细胞对于维持毛囊干细胞表型是否重要。分析在脂肪生成中具有遗传或脂肪诱导缺陷的小鼠，导致皮下脂肪细胞缺陷，和B.定义了毛发周期中的脂肪形成。2.通过a.确定皮下脂肪细胞是否在表皮伤口愈合中起作用。定义具有皮下脂肪细胞缺陷的小鼠中的伤口愈合反应，和B.定义在伤口愈合期间导致脂肪细胞再生的细胞机制。3.定义皮下脂肪细胞调节皮肤稳态的分子机制，使用脂肪细胞的体外测定来说明这些脂肪细胞在皮肤中表达信号分子的作用。患有脱发、毛干疾病或慢性伤口的患者可能会从这项研究中受益。