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IMPAIRED WOUND SIGNALING IN DIABETIC PERIODONTITIS

糖尿病牙周炎中伤口信号传导受损

基本信息

批准号：
6140126
负责人：
ANTHONY MICHAEL IACOPINO
金额：
$ 7.5万
依托单位：
MARQUETTE UNIVERSITY
依托单位国家：
美国
项目类别：
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

项目摘要

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.

糖尿病是美国的主要健康问题，约1300万人。五个“经典”并发症，在历史上与微血管病有关，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”，糖尿病的主要并发症，因为糖尿病患者表现出增加 PD的发生率/严重程度。糖尿病PD的细胞/分子基础是未知我们的初步数据表明PD和延迟性皮肤损伤 Haling是糖尿病中相同的全身性缺陷的表现。这种缺陷涉及以下细胞/分子信号的损伤：通过减少巨噬细胞生长因子/细胞因子的产生而损伤。我们有组建了一个代表基础科学、临床医学、医学和牙科来解决这个重要问题。主要待检验的假设是：1）糖尿病诱导的高脂血症/血脂异常干扰正常的细胞/分子通过改变巨噬细胞功能发出创伤信号;和2）这糖尿病引起的创伤信号损伤在对照组中是可逆的，血脂（低密度脂蛋白和甘油三酯）。临床、动物模型/体外系统，以及将使用细胞/分子分析来确定伤口信号，确定其与皮肤伤口愈合延迟和PD的关系。 PD将在全身性伤口愈合的背景下进行研究在面对持续的病理性损伤时表现为PD的缺陷，牙龈（菌斑）或皮肤伤口愈合延迟身体其他部位的周期性创伤。巨噬细胞将作为主要的细胞类型，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）及其能够通过释放许多重要的生长因子/细胞因子。巨噬细胞功能将采用免疫细胞化学技术，以证明表面标志物的存在抗原/受体，以及定量竞争性反向转录酶聚合酶链反应，原位杂交，和放射免疫测定方法来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，了解PD和伤口愈合延迟以及适当的/特殊的治疗。