IMPAIRED WOUND SIGNALING IN DIABETIC PERIODONTITIS

糖尿病牙周炎中伤口信号传导受损

• 批准号: 2132908
• 负责人: ANTHONY MICHAEL IACOPINO
• 金额: $ 9.1万
• 依托单位: BAYLOR COLLEGE OF DENTISTRY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2132908
• 关键词: antihyperlipoproteinemic agent; biological signal transduction; dental plaque; diabetes mellitus; gingivitis; human tissue; hyperlipidemia; immunocytochemistry; in situ hybridization; interleukin 1; laboratory rat; low density lipoprotein; macrophage; medical complication; periodontitis; platelet derived growth factor; polymerase chain reaction; radioimmunoassay; transforming growth factors; triglycerides; wound healing

Diabetes mellitus is a major health problem in the United States affecting approximately 13 million people. The five "classic" complications which have historically been associated with the condition are microangiopathy, neuropathy, nephropathy, macrovascular disease, and delayed wound healing. Recently, however, periodontal disease (PD) has been declared the "sixth" major complication of diabetes as diabetics demonstrate an increased incidence/severity of PD. The cellular/molecular basis for diabetic PD is unknown. Our preliminary data suggest that PD and delayed dermal wound haling are manifestations of the same general systemic deficit in diabetes. This deficit involves impairment of the cellular/molecular signal of wounding via reduced macrophage growth factor/cytokine production. We have assembled a team of investigators representing the basic sciences, clinical medicine, and dentistry to address this important issue. The major hypotheses to be tested are; 1) diabetes-induced hyperlipidemia/dyslipidemia interferes with the normal cellular/molecular signal of wounding by alteration of macrophage function; and 2) this diabetes-induced impairment of the wound signal is reversible with control of serum lipids (normalization of low density lipoproteins and triglycerides). Clinical, animal model/in vitro systems, and cellular/molecular analyses will be used to define the wound signal and determine its relationship to delayed dermal would healing and PD. PD will be investigated in the context of a generalized systemic wound healing deficit that manifests as PD in the face of constant pathologic wounding of the gingiva (bacterial plaque) or delayed dermal wound healing in instances of periodic traumatic wounding to other parts of the body. The macrophage will be targeted as the major cell type responsible for amplification/transduction of the wound signal because of its importance in the early phases of wound healing (inflammatory, granulation) and its ability to influence the wound environment via release of many important growth factors/cytokines. Macrophage function will be assessed utilizing immunocytochemical techniques to demonstrate the presence of surface marker antigens/receptors, as well as quantitative competitive reverse transcriptase polymerase chain reaction, in situ hybridization, and radioimmunoassay methodologies to quantitate expression and release of important growth factors/cytokines. It is anticipated that these cellular/molecular studies will provide information concerning defective tissue repair in diabetics that will have clinical relevance for the understanding of PD and delayed wound healing as well as applications of appropriate/specific therapies.

糖尿病是美国的一个主要健康问题，影响着 大约有1300万人。五大“经典”并发症 历史上与这种情况有关的是微血管病变， 神经病、肾病、大血管疾病和伤口愈合延迟。 然而，最近牙周病(PD)已被宣布为“第六大疾病”。 糖尿病的主要并发症糖尿病患者表现出增加 帕金森病的发生率/严重程度。糖尿病帕金森病的细胞/分子基础是 未知。我们的初步数据显示帕金森病和延迟性皮肤创伤 HALLING是糖尿病中相同的全身缺陷的表现。 这种缺陷涉及细胞/分子信号的损伤。 创伤通过减少巨噬细胞生长因子/细胞因子的产生。我们有 组建了一支研究团队，代表基础科学、临床 医学和牙科来解决这一重要问题。少校 需要检验的假设是：1)糖尿病诱发 高脂血症/血脂异常干扰正常细胞/分子 巨噬细胞功能改变所致的损伤信号；2) 糖尿病引起的创伤信号损害在对照组是可逆的 血脂(低密度脂蛋白正常化和 甘油三酯)。临床、动物模型/体外系统，以及 细胞/分子分析将被用来定义伤口信号和 确定其与皮肤愈合延迟和帕金森病的关系。警局会 在全身创伤愈合的背景下进行调查 在面对持续的病理性损伤时表现为帕金森病的缺陷 牙龈(菌斑)或皮肤伤口延迟愈合的情况 身体其他部位的周期性创伤性损伤。巨噬细胞 将被作为主要的细胞类型负责 创伤信号的放大/转导，因为它在 伤口愈合的早期阶段(炎症、肉芽形成)及其 通过释放许多重要的物质来影响伤口环境的能力 生长因子/细胞因子。巨噬细胞功能的评估将使用 免疫细胞化学技术证明表面标志物的存在 抗原/受体以及定量竞争反向 转录酶聚合酶链式反应、原位杂交和 放射免疫分析方法定量表达和释放 重要的生长因子/细胞因子。预计这些 细胞/分子研究将提供有关缺陷的信息 糖尿病患者的组织修复将具有临床意义 帕金森病与伤口延迟愈合的认识及应用 适当的/特定的治疗方法。