Pathophysiological profiling of vocal fold hyperkeratosis

项目总结/摘要 声带（VF）角化过度-上皮表面角蛋白的积聚导致临床 白斑病-主要使用破坏性技术进行治疗，有医源性损伤，纤维化和声音 损伤鉴于活检和病变切除的潜在发病率，迫切需要新的 检查和治疗VF白斑病的方法是非破坏性的， 疾病病理生理学在当前的应用中，我们提出了将推进这一点的转化研究 目标.我们的初步数据表明，必需营养素维生素A是上皮健康的关键调节因子， 并且全身性维生素A缺乏可直接导致角化过度。基于维生素的证据 A对VF星状细胞和上皮细胞生物学的重要性，以及它与VF角化过度的直接相关性，我们 提出了三个具体目标，将推动这一研究领域走向更大的临床适用性：（i） 评估VF角化过度患者的全身维生素A状态和病变组织病理学，以及（ii） 在大鼠模型中检查维生素A向正常和角化过度VF粘膜的运输和摄取。我们 首要目标是确定在糖尿病患者中补充维生素A是否有病理生理学依据。 VF角化过度的治疗。这种疗法将是变革性的--无论是作为一线治疗方法， 需要保守治疗的患者，以及需要手术治疗的患者的辅助治疗 治疗是指。

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.