Apoptosis Signaling in Vocal Fold Epithelium in Response to Acute Phonotrauma

声带上皮细胞凋亡信号对急性声损伤的反应

• 批准号: 8981151
• 负责人: Carolyn K. Novaleski
• 金额: $ 3.75万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8981151
• 关键词: Acute; Address; Apical; Apoptosis; Apoptotic; Area; Basement membrane; Benign; Biological; Biological Assay; Biomechanics; Cell surface; Cells; Communication; Communication impairment; Complex; Consult; Cyst; DNA Nucleotidylexotransferase; Development; Diagnosis; Disease; Dose; Dysphonia; Epithelial; Epithelial Cells; Epithelium; Event; Fostering; Foundations; Gene Expression; Impairment; Individual; Injury; Intervention; Investigation; Knowledge; Label; Laboratories; Larynx; Lesion; Maintenance; Measures; Mentors; Molecular; National Institute on Deafness and Other Communication Disorders; National Research Service Awards; Nodule; Organism; Patients; Phenotype; Polyps; Prevention; Proteins; Quality of life; Refractory; Research; Research Personnel; Research Training; Resources; Scientist; Series; Signal Pathway; Signal Transduction; Solid; Staining method; Stains; Strategic Planning; Stratified Squamous Epithelium; Stress; Structure; Surface; Testing; Tight Junctions; Time; Training; Transcript; Transferase; Transmission Electron Microscopy; Treatment Cost; United States; Voice; Voice Disorders; Work; career development; caspase-3; cost; experience; improved; innovation; novel; occludin; pre-doctoral; programs; public health relevance; response; theories; therapeutic development; vibration; vocal cord

 DESCRIPTION (provided by applicant): It is estimated that the annual cost of the treatment for voice disorders in the United States is between $11.9- 13.5 billion. A significant contributor o the development of benign vocal fold disease, such as nodules, polyps, and cysts, is phonotrauma. In severe cases, benign vocal fold disease can result in dysphonia with reduced overall quality of life and compromised communication function. The vocal fold epithelial barrier is critical in maintaining the integrity of the vocal folds. During acute episodes of phonotrauma, the epithelial barrier structure and function are severely compromised. The current strategic plan of the National Institute on Deafness and Other Communication Disorders has acknowledged that laryngeal structure and function changes and mechanisms underlying disorders resulting from phonotrauma are priority areas of research. The objective of the proposed research is to test a theory regarding how vocal fold epithelial barrier disruption occurs. The theory reasons that the biomechanical stresses during phonotrauma signal apoptosis, or programmed cell death. Preliminary studies from our laboratory demonstrate that apoptosis signaling occurs along the apical cell surface of the vocal fold epithelium after acute phonotrauma. This finding has led to the overarching hypothesis that apoptosis signaling in the vocal fold epithelium increases with longer time-doses and larger magnitude-doses of vibration exposure. If this hypothesis is supported, the proposed research will provide empirical evidence for a specific signaling pathway involved in vocal fold epithelial barrier disruption. The specific aim of the proposed research is (1) to measure the effects of increasing time-dose and magnitude-dose of vibration exposure on apoptosis signaling in the vocal fold epithelium. This aim will be addressed using a number of approaches that are highly innovative to this field, including terminal deoxynucleotidyl transferase dUTP nick end labeling assay staining, caspase-3 staining, and transmission electron microscopy. If the hypothesis is correct, findings will provide novel evidence for a specific mechanism that is responsible for the maintenance of the vocal fold epithelial barrier. It is anticipated that this work will provide a solid foundation of critical knowledge for a programmatic line of research focusing on the development of therapeutic approaches to regulate apoptosis and preserve the integrity of the vocal fold epithelial barrier in patients with benign vocal fold disease.

 描述（由申请人提供）：据估计，美国每年用于治疗嗓音障碍的费用在119亿至135亿美元之间。良性声带疾病，如结节、息肉和囊肿的发展的一个重要贡献者是声音创伤。在严重的情况下，良性声带疾病可导致发声困难，降低整体生活质量和沟通功能受损。声带上皮屏障对维持声带的完整性至关重要。在急性发作的声音创伤，上皮屏障结构和功能严重受损。国家耳聋和其他交流障碍研究所目前的战略计划承认，喉结构和功能的变化以及声音创伤引起的疾病的机制是研究的优先领域。这项研究的目的是测试一个关于声带上皮屏障破坏是如何发生的理论。该理论认为，生物力学应力在声创伤信号细胞凋亡，或程序性细胞死亡。我们实验室的初步研究表明，细胞凋亡信号发生沿着急性声创伤后声带上皮的顶端细胞表面。这一发现导致了一个总体假设，即声带上皮细胞凋亡信号随着振动暴露的时间-剂量和幅度-剂量的增加而增加。如果这一假设得到支持，拟议的研究将提供经验证据，一个特定的信号通路参与声带上皮屏障破坏。具体 本研究的目的是（1）研究振动暴露时间-剂量和强度-剂量对声带上皮细胞凋亡信号的影响。这一目标将使用一些方法，是高度创新的这一领域，包括末端脱氧核苷酸转移酶dUTP缺口末端标记试验染色，半胱天冬酶-3染色，透射电子显微镜。如果假设是正确的，研究结果将提供新的证据，一个特定的机制，负责维持声带上皮屏障。预计这项工作将提供一个坚实的基础，关键的知识，重点是发展的治疗方法，以调节细胞凋亡和维护声带上皮屏障的良性声带疾病患者的研究纲领线。