Exploring hair follicle-associated functions in normal and ichthyotic skin

探索正常和鱼鳞病皮肤的毛囊相关功能

基本信息

批准号：
10630934
负责人：
Sunny Y Wong
金额：
$ 39.82万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-06-01 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10630934
关键词：
Acne Affect Anatomy Carrier Proteins Cell Death Cell Differentiation process Cell membrane Cell physiology Cells Cytoplasmic Granules Defect Disease Enterobacteria phage P1 Cre recombinase Environment Epidermis Gene Expression Gene Expression Profile Grant Hair Hair follicle structure Harlequin Ichthyosis Hidradenitis Suppurativa Homeostasis Hyperplasia Ichthyoses Immunocompetent In Vitro Keratosis Knowledge Learning Link Lipids Mediating Mus Mutant Strains Mice Mutate Organelles Outcome Patients Peptide Hydrolases Phenotype Physiology Play Process Protein Family Proteins Role Sebum Signal Transduction Site Skin Stratum corneum Structure Surface Testing Time Work behavior influence extracellular insight keratinocyte keratinocyte differentiation member molecular domain mouse model novel novel therapeutics response skin barrier skin disorder stem cell population tool wound

项目摘要

Project Summary / Abstract Our skin is a multi-layered structure that acts as a protective barrier against the environment. Barrier function is typically associated with the surface of the skin; however, it is currently unclear whether the hair follicle also forms a barrier. Here, we have generated mice that enable spatially and temporally restricted deletion of the lipid transporter ABCA12, which is mutated in patients with harlequin ichthyosis (HI), the most severe skin barrier disease. We will utilize these mice as tools to study the contributions of the hair follicle to skin homeostasis, while examining how hair follicle-related processes are perturbed in HI. We hypothesize that the hair follicle may affect both normal and ichthyotic skin in the following 4 ways: 1) The upper hair follicle may directly provide barrier function. 2) The hair follicle may influence the behavior of the adjacent epidermis non- cell autonomously. 3) The upper hair follicle is likely a site of rapid desquamation that allows for the release of sebum. 4) The upper hair follicle may assume a wound-like state and contribute cells to the epidermis upon barrier disruption. Altogether, these studies will contribute fundamental knowledge to our understanding of the upper hair follicle domain, a poorly studied region of the skin that is perturbed in diseases such as acne, hidradenitis suppurativa and keratosis pilaris. At the same time, this work will also consider HI from a novel angle, with a focus on the hair follicle. Finally, our studies will characterize a viable, immunocompetent mouse model of HI to explore novel therapies.

项目概要/摘要我们的皮肤是一个多层结构，可以作为抵御环境的保护屏障。屏障功能通常与皮肤表面有关；然而，目前尚不清楚毛囊是否也形成障碍。在这里，我们生成了能够在空间和时间上限制性删除脂质转运蛋白 ABCA12，在患有丑角鱼鳞病 (HI)（最严重的皮肤病）的患者中发生突变屏障病。我们将利用这些小鼠作为工具来研究毛囊对皮肤的贡献体内平衡，同时检查毛囊相关过程在 HI 中如何受到干扰。我们假设毛囊可能通过以下 4 种方式影响正常和鱼鳞病皮肤： 1) 上毛囊可能会影响正常皮肤和鱼鳞病皮肤。直接提供屏障功能。 2) 毛囊可能会影响邻近表皮的行为细胞自主地。 3) 上毛囊可能是快速脱屑的部位，可以释放皮脂。 4) 上毛囊可能呈现伤口状状态，并在表皮上贡献细胞屏障破坏。总而言之，这些研究将为我们理解上毛囊区，这是一个研究不足的皮肤区域，容易受到痤疮等疾病的影响，化脓性汗腺炎和毛周角化症。同时，本作也会考虑小说中的HI 角度，重点关注毛囊。最后，我们的研究将描述一种存活的、具有免疫功能的小鼠的特征 HI 模型探索新疗法。