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

• 批准号: 10415368
• 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
• 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/10415368
• 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

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.

项目摘要/摘要 我们的皮肤是一个多层结构，起到了抵御环境的保护屏障的作用。屏障函数 通常与皮肤表面有关；然而，目前尚不清楚毛囊是否也 形成了一道屏障。在这里，我们已经生成了能够在空间和时间上受限地删除 脂转运蛋白ABCA12，在最严重的皮肤小丑鱼鳞病(HI)患者中发生突变 障碍症。我们将利用这些小鼠作为工具来研究毛囊对皮肤的贡献 动态平衡，同时研究在HI中毛囊相关的过程是如何被干扰的。我们假设 毛囊可能通过以下4种方式影响正常皮肤和鱼鳞病皮肤：1)上毛囊可能 直接提供屏障功能。2)毛囊可能会影响邻近非表皮的行为 细胞自主性。3)上毛囊可能是快速脱屑的部位，允许释放 皮脂。4)上毛囊可能呈伤口样状态，并为表皮提供细胞。 障碍物破坏。总之，这些研究将有助于我们理解 上毛囊区域，这是皮肤上一个研究较少的区域，受到粉刺等疾病的困扰， 化脓性汗腺炎和毛发角化病。同时，这部作品还将从一部小说中考虑HI 角度，重点放在毛囊。最后，我们的研究将确定一种具有免疫能力的存活小鼠的特征 HI模型，探索新的治疗方法。