Inflammation and Fibrosis of the Vocal Folds

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音困难。目前对这些具有挑战性的患者的治疗是不令人满意的，可能是由于对声带损伤和修复的生化过程的了解有限。考克斯-2/PGE 2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，我们的实验室和其他人已经报道了考克斯-2和PGE 2在声带损伤中的上调，我们现在试图扩大这些发现，以确定该信号通路在声带损伤和修复中的调节作用。在研究这一途径，我们将研究关键的时间和分子开关声带瘢痕，适合药理学操作。此外，我们将获得初步的数据，药理学抑制考克斯-2作为一种手段，以促进较少的纤维化反应后声带损伤。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。

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.