Hair follicle neogenesis in response to wounding

受伤时的毛囊新生

• 批准号: 8505685
• 负责人: GEORGE COTSARELIS
• 金额: $ 34万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-12 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8505685
• 关键词: Accounting; Adipose tissue; Adult; Alopecia; Area; Back; Biological Models; Biology; Bypass; Calculi; Cells; Cicatrix; Dermal; Dermis; Development; Developmental Biology; Embryo; Epidermis; Event; Excision; Fatty acid glycerol esters; Fibroblasts; Fibrosis; Funding; Future; Gene Expression; Goals; Hair; Hair follicle structure; Healed; Health; Human; Immune; Immune system; Immunodeficient Mouse; Knockout Mice; Maps; Molecular; Mus; Myofibroblast; Natural regeneration; Pathway interactions; Play; Population; Psyche structure; Regenerative Medicine; Role; Sebaceous Glands; Signal Transduction; Skin; T-Lymphocyte; Testing; Thick; Time; Tissues; Tomatoes; Transgenic Mice; Transgenic Organisms; Translating; Wild Type Mouse; Work; Wound Healing; Xenograft Model; appendage; base; healing; improved; inhibitor/antagonist; innovation; insight; mature animal; overexpression; promoter; public health relevance; regenerative; repaired; response; skin disorder; skin regeneration; skin xenograft; smoothened signaling pathway; stem cell niche; tongue papilla; wound

DESCRIPTION (provided by applicant): The long-term goal of this project is to develop better treatments for wounds, alopecias and other degenerative skin disorders by elucidating the cellular and molecular mechanisms of skin regeneration following wounding. We demonstrated that adult mice have the capacity to regenerate hair follicles, sebaceous glands and fat following a full thickness wound. We have evidence that Wnt, Fgf, Hh pathways and gamma/delta T cells are vital players controlling this wound induced hair follicle neogenesis (WIHN). We hypothesize that manipulation of these molecular pathways at the right time and place will convert non-regenerative tissue into regenerative tissue with the ability to form hair follicles, sebaceous glands and fat in response to wounding. To test this hypothesis, we will determine: 1. The role of dermal Wnt/ss-catenin signaling in hair follicle neogenesis using transgenic and conditional knockout mice, 2. The cellular origin of nascent hair follicles in the wound using promoters targeting fibroblasts, myofibroblasts, hair follicle dermal papilla and other dermal subpopulations for lineage analysis, 3. The role of sonic hedgehog signaling in the ability to coax healing wounds to regenerate rather than scar. Human skin xenografted to immunodeficient mice will be studied for its ability to respond with follicular neogenesis to Wnt and/or Shh activation. Ultimately, our findings will yield insights into scarless wound healing tht have implications for understanding skin biology and developing future treatments for wounds, alopecia and other degenerative skin disorders.

描述（由申请人提供）：该项目的长期目标是通过阐明创伤后皮肤再生的细胞和分子机制，开发更好的创伤、脱发和其他退行性皮肤病治疗方法。我们证明了成年小鼠在全层创伤后有能力再生毛囊、皮脂腺和脂肪。我们有证据表明，Wnt，Fgf，Hh通路和γ/δ T细胞是控制这种伤口诱导的毛囊新生（WIHN）的重要参与者。我们假设，在适当的时间和地点操纵这些分子通路，将使非再生组织转化为具有形成毛发能力的再生组织 毛囊、皮脂腺和脂肪对创伤的反应。为了验证这个假设，我们将确定：1。使用转基因和条件性基因敲除小鼠，真皮Wnt/β-连环蛋白信号传导在毛囊新生中的作用，2。使用靶向成纤维细胞、肌成纤维细胞、毛囊毛乳头和其他真皮亚群的启动子进行谱系分析，3.音速刺猬信号在诱导愈合伤口再生而不是留下疤痕的能力中的作用。 将研究异种移植到免疫缺陷小鼠的人皮肤对Wnt和/或Shh激活的滤泡新生反应的能力。最终，我们的研究结果将产生对无瘢痕伤口愈合的见解，这对理解皮肤生物学和开发未来的伤口，脱发和其他退行性皮肤疾病的治疗方法具有重要意义。