Growth Factors in Recurrent Aphthous Stomatitis

复发性口疮性口炎中的生长因子

• 批准号: 7990993
• 负责人: Lorena Baccaglini
• 金额: $ 5.92万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2012-05-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990993
• 关键词: Adverse effects; Affect; Age Distribution; Agreement; American; Aphthous Stomatitis; Applications Grants; Autoimmune Process; Biological Markers; Caliber; Chemicals; Clinical; Clinical Research; Clinical Trials; Data; Development; Disease; Drug Delivery Systems; Employee Strikes; Endocrine; Etiology; Fostering; Foundations; Goals; Growth; Growth Factor; Immune system; Impaired wound healing; Individual; Insulin; Insulin-Like Growth Factor I; Leptin; Lesion; Level of Evidence; Life; Link; Literature; Lymphocyte Activation; Mechanics; Medical; Minor; Modern Medicine; Oral mucous membrane structure; Pain; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Physiologic pulse; Play; Population Study; Prevalence; Prevention; Process; Property; Publishing; Quality of life; Reaction; Recording of previous events; Recurrence; Research; Risk Factors; Role; Scientist; Serum; Source; Staging; Stimulus; Testing; Translational Research; Trauma; Ulcer; Up-Regulation; Wound Healing; design; driving force; effective therapy; evidence base; experience; immune activation; innovation; microorganism; public health relevance; research study; smoking cessation; theories; therapy development

DESCRIPTION (provided by applicant): Recurrent Aphthous Stomatitis (RAS) is a very common ulcerative oral mucosal disease of unknown etiology. Over 100 million Americans experience these painful ulcers at some point in life. The ulcers may reach half inch in diameter and can last several weeks, affecting patients' quality of life. The lack of understanding of the exact etiology and mechanism of ulcer formation in patients afflicted by this very painful condition has hampered the development of effective therapies. In order to plan and implement successful clinical trials leading to the development of better drugs for our patients we must first identify the cause of this disease. Most scientists agree that the immune system is activated in RAS. However, there is no agreement as to what leads to its activation and ultimately to the development of RAS. Modern medicine has identified intense cross-talks between the endocrine and immune system. In particular, growth factors, such as IGF-1 and related biomarkers, have been shown to regulate the immune system and also wound healing. In two separate published population studies we have found a striking overlap in the age distribution of RAS prevalence and circulating levels of these growth factors. These data, however, do not directly associate RAS and serum levels of growth factors within the same individuals. Our central hypothesis is that excessive levels of IGF-1 are the primary source of immune activation and impaired wound healing in RAS patients. The specific objective of this grant application is to identify links between IGF-1 (and IGF-1-related growth factors) levels and RAS prevalence through secondary analyses of existing national data. Specific Aim 1 is to compare the odds of having RAS now vs. having had recent RAS for each increment in circulating growth factors levels (IGF-1, leptin and insulin). Specific Aim 2 is to compare the odds of having vs. not having had a recent history of RAS for each increment in circulating growth factors levels (IGF-1, leptin and insulin). These results will provide the first evidence that the levels of these growth factors are closely associated with the presence of painful aphthous ulcers. The results of these analyses will create the foundation for R01-level clinical and translational research studies focused on growth factors as the primary driving force leading to RAS formation. PUBLIC HEALTH RELEVANCE: Recurrent Aphthous Stomatitis (RAS; also known as canker sores) is a very common and painful disease of unknown cause that occurs primarily during growth. We have noted a remarkable overlap between RAS and certain growth factors that regulate wound healing, suggesting that this could be the pathway through which RAS develops. The identification of the specific mechanism that leads to RAS formation would open the door to the development of more targeted drugs, expected to have fewer side effects and greater efficacy, for patients suffering from this condition.

描述（申请人提供）：复发性口腔溃疡性口腔炎（RAS）是一种非常常见的溃疡性口腔黏膜疾病，病因不明。超过1亿的美国人在生活的某个阶段经历过这些痛苦的溃疡。溃疡直径可达半英寸，持续数周，影响患者的生活质量。由于缺乏对患者溃疡形成的确切病因和机制的了解，这种非常痛苦的疾病阻碍了有效治疗方法的发展。为了计划和实施成功的临床试验，从而为我们的病人开发更好的药物，我们必须首先确定这种疾病的原因。大多数科学家都认为，RAS激活了免疫系统。然而，是什么导致了它的激活并最终导致了RAS的发展，目前还没有达成一致意见。现代医学已经确认了内分泌和免疫系统之间的密切联系。特别是，生长因子，如IGF-1和相关的生物标志物，已被证明可以调节免疫系统和伤口愈合。在两项独立发表的人口研究中，我们发现RAS患病率的年龄分布和这些生长因子的循环水平有显著的重叠。然而，这些数据并没有将RAS和同一个体的血清生长因子水平直接联系起来。我们的中心假设是，过量的IGF-1水平是RAS患者免疫激活和伤口愈合受损的主要来源。该资助申请的具体目标是通过对现有国家数据的二次分析，确定IGF-1（以及IGF-1相关生长因子）水平与RAS患病率之间的联系。特异性目的1是比较当前和近期RAS患者在循环生长因子水平（IGF-1、瘦素和胰岛素）每增加一次的可能性。具体目标2是比较有和没有RAS近期病史的几率，因为循环生长因子水平（IGF-1、瘦素和胰岛素）的每一次增加。这些结果将提供第一个证据，证明这些生长因子的水平与疼痛性阿弗顿溃疡的存在密切相关。这些分析结果将为r01水平的临床和转化研究奠定基础，重点关注生长因子作为导致RAS形成的主要驱动力。