Pathophysiological profiling of vocal fold hyperkeratosis

项目摘要/摘要 声带(VF)角化过度--上皮表面角蛋白积聚导致临床 白斑-主要使用有医源性损伤、纤维化和声音风险的破坏性技术进行治疗 减损。鉴于活组织检查和病变切除的潜在发病率，迫切需要新的 非破坏性和根植性VF白斑疾病的治疗和治疗方法 疾病病理生理学。在目前的应用中，我们建议进行翻译研究，以推动这一点 进球。我们的初步数据表明，必需的营养物质维生素A是上皮健康的关键调节因素 系统性维生素A缺乏会直接导致角化过度。基于维他命的证据 A对VF星状细胞和上皮细胞生物学的重要性，以及它与VF过度角化的直接关系，我们 提出三个具体目标，通过以下方式推动这一研究领域向更大的临床适用性迈进： 评估VF过度角化患者的全身性维生素A状态和病变组织病理学，以及(Ii) 在大鼠模型中检测维生素A向正常和过度角化的VF粘膜的转运和摄取。我们的 首要目标是确定补充维生素A是否有病理生理学基础。 VF角化过度的治疗。这样的疗法将是变革性的-既作为治疗的第一线方法 需要保守治疗的患者，以及手术患者的辅助治疗 治疗是有意义的。

Project Summary/Abstract Vocal fold (VF) hyperkeratosis – an accumulation of epithelial surface keratin resulting in clinical leukoplakia – is primarily managed using destructive techniques that risk iatrogenic injury, fibrosis, and voice impairment. Given the potential morbidity of biopsy and lesion removal, there is a compelling need for new approaches to the workup and treatment of VF leukoplakic disorders that are non-destructive and grounded in disease pathophysiology. In the current application, we propose translational research that will advance this goal. Our preliminary data indicate that the essential nutrient vitamin A is a key regulator of epithelial health and that systemic vitamin A deficiency can directly contribute to hyperkeratosis. Based on evidence of vitamin A’s importance to VF stellate and epithelial cell biology, and its direct relevance to VF hyperkeratosis, we propose three Specific Aims that will advance this research area towards greater clinical applicability by: (i) assessing the systemic vitamin A status and lesion histopathology of patients with VF hyperkeratosis, and (ii) examining vitamin A trafficking to, and uptake by, normal and hyperkeratotic VF mucosa in a rat model. Our overarching goal is to determine if there is a pathophysiologic rationale for vitamin A supplementation in the treatment of VF hyperkeratosis. Such a therapy would be transformative – both as a first-line approach for patients who require conservative management, as well as an adjuvant therapy in patients for whom surgical treatment is indicated.