Retinoic acid synthesis induced by noncoding dsRNA controls Regeneration

非编码 dsRNA 诱导的视黄酸合成控制再生

• 批准号: 10025168
• 负责人: Luis Andres Garza
• 金额: $ 46.46万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-25 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10025168
• 关键词: Affect; Apocrine Glands; Biological Models; Biology; Blood Vessels; Chemicals; Cicatrix; Combined Modality Therapy; Data; Dermatology; Development; Diagnostic; Double-Stranded RNA; Eccrine Glands; Embryonic Development; Enzymes; Excision; Fascia; Feedback; Fibrosis; Frequencies; Future; Gene Expression; Gene Proteins; Genetic Transcription; Geography; Goals; Grant; Hair; Hair follicle structure; Health; Heart; Homeostasis; Human; Injury; Knockout Mice; Lasers; Learning; Ligands; Location; Lung; Mass Spectrum Analysis; Molecular Chaperones; Mus; Myocardial Infarction; Natural regeneration; Nerve; Pathology; Pathway interactions; Production; Proteomics; Pulmonary Fibrosis; Recurrence; Research; Retina; Retinoic Acid Receptor; Role; Signal Transduction; Skin; Skin injury; Spottings; Structure; TLR3 gene; Testing; Therapeutic; Tissues; Topical application; Translating; Tretinoin; Untranslated RNA; Wild Type Mouse; appendage; base; cell type; chronic wound; healing; heart function; human subject; in vivo; inhibitor/antagonist; injured; insight; keratinocyte; novel therapeutics; prevent; protein expression; receptor; response; retinoic acid receptor alpha; skin regeneration; skin wound; transcriptomics; wound; wound healing

Project Summary Abstract The long term objective of the proposed research is to learn what controls whether injuries heal with scarring/fibrosis versus full regeneration of lost structures. The human health burden of fibrosis and scarring is enormous and affects every tissue from heart (lost heart function after a myocardial infarction) to lung (idiopathic lung fibrosis). Enhancing regeneration could prevent for example the almost universal recurrence of chronic wounds in the exact location where they previously appeared. We use the Wound Induced Hair Neogenesis (WIHN) model system where in the center of excisional wounds in mice a variable amount of regeneration occurs and de novo hair follicles form in a recapitulation of embryogenesis. The goal of this grant is to understand the factors which control the frequency of regeneration. We will directly test the mechanism and the ability for candidate molecules which enhance regeneration in mice and in human subjects. The results of this grant promise to help define new treatments and diagnostics to enhance regeneration and wound healing.

项目摘要摘要 这项拟议中的研究的长期目标是了解是什么控制了创伤是否会愈合 瘢痕形成/纤维化与完全再生丢失的结构。纤维化和疤痕造成的人类健康负担是 巨大，影响从心脏(心肌梗死后丧失心脏功能)到肺的每一个组织 (特发性肺纤维化)。例如，加强再生可以防止几乎普遍的癌症复发 在他们之前出现的确切位置上的慢性伤口。我们用伤口诱导的毛发 新生(WIHN)模型系统，其中在小鼠切除伤口的中心 再生发生并形成新生毛囊，这是胚胎发生的重演。这笔赠款的目的是 就是了解控制再生频率的因素。我们将直接测试这个机制 以及促进小鼠和人类受试者再生的候选分子的能力。结果是 这笔赠款承诺帮助确定新的治疗方法和诊断方法，以促进再生和伤口 治愈。