Inflammation and Fibrosis of the Vocal Folds

声带炎症和纤维化

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：在许多情况下，声带损伤会导致纤维化和发声困难。目前对这些具有挑战性的患者的治疗方法并不令人满意，可能是由于对声带损伤和修复的生化过程的了解有限。 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实验室报告了声带损伤中 COX-2 和 PGE2 的上调，我们现在寻求扩展这些发现，以确定该信号通路在声带损伤和修复中的调节作用。在检查该通路时，我们将检查与声带疤痕相关的关键时间和分子开关，这些开关适合药理学操作。此外，我们将获得有关 COX-2 药理学抑制的初步数据，作为减少声带损伤后纤维化反应的一种手段。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：声带纤维化与显着的发病率相关。目前的提案旨在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疗法。