Inflammation and Fibrosis of the Vocal Folds

声带炎症和纤维化

• 批准号: 7885430
• 负责人: Ryan Comfort Branski
• 金额: $ 1.44万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-09 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7885430
• 关键词: Address; Agonist; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Beds; Bilateral; Biochemical Process; Cell Line; Cells; Cicatrix; Complex; Coxibs; Cyclic AMP Receptors; Data; Dinoprostone; Dose; Dysphonia; Fetus; Fibroblasts; Fibrosis; Healed; Human; Inflammation; Inflammatory; Inflammatory Response; Injury; Interleukins; Investigation; Laboratories; Lamina Propria; Larynx; Lesion; Literature; Measures; Mediating; Modeling; Molecular; Morbidity - disease rate; Nature; Nuclear Translocation; Outcome; Paracrine Communication; Pathway interactions; Patients; Phase; Phenotype; Principal Investigator; Production; Rattus; Reporting; Role; Severities; Signal Pathway; Signal Transduction; Structure; Techniques; Time; Tissues; Transcriptional Regulation; Transforming Growth Factors; Up-Regulation; Wound Healing; autocrine; base; clinical application; cyclooxygenase 2; cytokine; healing; injured; injury and repair; insight; novel; patient population; programs; public health relevance; regenerative; repaired; response; vocal cord; wound

DESCRIPTION (provided by applicant): In many cases, injury to the vocal fold results in fibrosis and dysphonia. Current therapies for these challenging patients are unsatisfactory, likely due to limited insight into the biochemical processes underlying vocal fold injury and repair. COX-2/PGE2 signaling is upregulated in fibrotic lesions in many tissues and has emerged as a target for antifibrotic therapy. In the larynx, our laboratory and others have reported upregulation of COX-2 and PGE2 in vocal fold injury and we now seek to expand these findings to determine the regulatory role of this signaling pathway in vocal fold injury and repair. In examining this pathway, we will examine key temporal and molecular switches related to vocal fold scarring that are suitable for pharmacological manipulation. Furthermore, we will obtain preliminary data regarding pharmacological inhibition of COX-2 as a means to facilitate a less fibrotic response following vocal fold injury. These findings are significant and have the potential for far-reaching scientific and clinical applications. Public Health Relevance: Fibrosis of the vocal folds is associated with significant morbidity. The current proposal seeks to investigate one regulatory signaling pathway in order to develop novel therapies for this challenging patient population.

描述(申请人提供)：在许多情况下，声带损伤会导致纤维化和发音困难。目前对这些具有挑战性的患者的治疗并不令人满意，可能是因为对声带损伤和修复背后的生化过程缺乏了解。COX-2/PGE2信号在许多组织的纤维化病变中上调，并已成为抗纤维化治疗的靶点。在喉部，我们的实验室和其他人已经报道了COX-2和PGE2在声带损伤中的上调，我们现在试图扩大这些发现，以确定这一信号通路在声带损伤和修复中的调节作用。在研究这一途径时，我们将检查与声带瘢痕形成相关的关键的时间和分子开关，这些开关适合于药物操作。此外，我们将获得关于药物抑制COX-2的初步数据，以此作为促进声带损伤后较少纤维化反应的手段。这些发现意义重大，具有深远的科学和临床应用潜力。 公共卫生相关性：声带纤维化与显著的发病率有关。目前的提案试图研究一种调节信号通路，以便为这一具有挑战性的患者群体开发新的治疗方法。