SCOR in Pathobiology of Fibrotic Lung Disease

SCOR 在纤维化肺疾病病理学中的应用

• 批准号: 6620068
• 负责人: Galen B Toews
• 金额: $ 202.25万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-12-26 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620068
• 关键词: pathologic process; pulmonary fibrosis /granuloma

(Applicant's Abstract) The long-term objective of this SCOR is to further our understanding of the pathogenesis of the idiopathic interstitial pneumonias (UP). A clear understanding of the pathogenesis of these diseases is required to develop new treatment strategies. The central hypothesis for this SCOR proposal is: Local alterations in the elaboration of effector molecules or in the expression of receptors by inflammatory, epithelial, and mesenchymal cells create an alveolar microenvironment that favors the fibroproliferative response rather than normal repair. Such dysregulation in autocrine and/or paracrine regulatory loops determine susceptibility to and expression of fibrotic lung disease. In each project of this SCOR, this central hypothesis will be extended to define the role of a specific set of mediators and/or receptors in pathobiological processes relevant to fibrogenesis. These mediators include cytokines, chemokines, elcosanoids and proteases. Studies will utilize animal models of fibrosis and/or patients with HP to examine abnormalities in cells and tissues and the role of each mediator in the pathobiology of fibrosis. An important feature is the mechanistic insights these studies provide to the use of standard (prednisone, azathioprine + prednisone) and novel (5-lipoxygenase inhibitor, zileuton) therapeutic agents under investigation in our ongoing clinical project. This SCOR will take a multi-disciplinary approach to testing these hypotheses. The expertise of investigators trained in Internal Medicine, Pathology, Cell and Molecular Biology, Biochemistry, and Biostatistics will be utilized. The strength of this proposal are the investigators long-standing interests in fibrotic lung disease, a proven commitment to collaborative research by both clinicians and basic scientists, access to a large population of IIP patients, and extraordinary institutional resources of biomedical Research. This SCOR capitalizes on a bench to bedside continuum of research that is crucial to translate advances in basic research to the clinical arena.

（申请人的摘要）本SCOR的长期目标是进一步促进我们的 对特发性间质性肺炎发病机制的认识 （UP）。需要对这些疾病的发病机制有清楚的认识 开发新的治疗策略。该SCOR的核心假设是 建议是：在效应分子的加工或在细胞中的局部改变， 炎症细胞、上皮细胞和间质细胞的受体表达 创造有利于纤维增生的肺泡微环境 而不是正常的修复。这种自分泌和/或 旁分泌调节环决定了 纤维化肺病在SCOR的每个项目中， 将扩大到界定一组特定调解人的作用和/或 受体在与纤维形成相关的病理生物学过程中的作用。这些 介质包括细胞因子、趋化因子、类依可生素和蛋白酶。研究 将利用纤维化动物模型和/或HP患者来检查 细胞和组织中的异常以及每个介质在细胞和组织中的作用。 纤维化的病理生物学一个重要的特点是机械的见解 这些研究提供了使用标准（泼尼松、硫唑嘌呤+ 泼尼松）和新的（5-脂氧合酶抑制剂，齐留通）治疗剂 在我们正在进行的临床项目中进行研究。 该SCOR将采用多学科方法来测试这些假设。 接受过内科、病理学、细胞学培训的研究者的专业知识 分子生物学，生物化学和生物统计学将被利用。的 这一建议的力量是调查人员的长期利益， 肺纤维化疾病，这是双方合作研究的一项承诺， 临床医生和基础科学家，接触大量的IIP患者， 和卓越的生物医学研究机构资源。这个scar 利用从实验室到床边的连续研究， 将基础研究的进展转化为临床竞技场。