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Pulmonary Myofibroblast Growth and Proliferation

肺肌成纤维细胞的生长和增殖

基本信息

批准号：
6406421
负责人：
Nancy Ayers Rice
金额：
$ 3.48万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-01-01 至
项目状态：
未结题

项目摘要

DESCRIPTION (provided by applicant): Myofibroblasts are unique cells possessing ultrastructural characteristics of both muscle an non-muscle cells. Under normal conditions, myofibroblasts are essential for the formation of functional adult tissues and are intimately involved in tissue homeostasis and wound healing. Activation of myofibroblasts is characterized by an increase in alpha smooth muscle actin expression, proliferation and contractility. It is their persistence during injury, however, that has implicated them in many disease states including fibrosis. We have found that these cells also express multiple structural and regulatory skeletal muscle proteins, including MyoD, in response to cytokine treatment. Despite the expression of MyoD, an inhibitor of the cell-cycle, myofibroblasts do not terminaly differentiate. Because lymphangioleiomyomatosis (LAM) cells and myofibroblasts share many cellular phenotypes, we propose that myofibroblasts contribute to the pathogenesis of LAM. Therefore, the goal of this fellowship is to determine the cellular and molecular phenotypes of pulmonary myofibroblasts and subsequently, to elucidate the intracellular mechanisms responsible for growth and proliferation in normal and diseased lung. This project has three related aims directed at this goal. (1) The molecular and cellular characteristics of isolated pulmonary myofibroblasts will be determined in order to establish a basis for evaluating changes that occur in these cells in response to injury. (2) The phenotypic cellular and molecular changes that occur in myofibroblasts as a result of the induction of pulmonary fibrosis will be determined. This information will be invaluable in elucidating the relationship between myofibroblast activation and disease. (3) Finally, once we have fully characterized myofibroblasts in normal and diseased lung we will begin to elucidate the molecular mechanisms responsible for their proliferation. Ultimately these studies will provide the foundation for future investigations in human LAM tissue and will be critical in establishing the link between LAM cell proliferation and the development of new therapeutics.

描述(申请人提供)：肌成纤维细胞是一种独特的细胞，具有肌肉和非肌肉细胞的超微结构特征。在……下面正常情况下，肌成纤维细胞是形成功能性成体组织，与组织动态平衡和创伤密切相关治愈。肌成纤维细胞激活的特征是α增加。平滑肌肌动蛋白的表达、增殖和收缩。这是他们的然而，在受伤期间的坚持不懈，这使他们与许多疾病有关包括纤维化在内的国家。我们发现这些细胞也表达多个结构和调节骨骼肌蛋白质，包括MyoD，作为响应到细胞因子治疗。尽管有MyoD的表达，MyoD是一种细胞周期中，肌成纤维细胞不进行终末分化。因为淋巴管肌瘤病(LAM)细胞和肌成纤维细胞共享许多细胞表型，我们认为肌成纤维细胞参与了骨肉瘤的发病机制。林。因此，这个奖学金的目标是确定细胞和肺肌成纤维细胞的分子表型及其意义正常人生长和增殖的细胞内机制和病变的肺部。该项目针对这一目标有三个相关的目标。 (1)分离的肺泡巨噬细胞的分子和细胞特征将对肌成纤维细胞进行测定，以建立评估的基础这些细胞对损伤的反应所发生的变化。(2)表型肌成纤维细胞中发生的细胞和分子变化肺纤维化的诱导性将被确定。这一信息将是在阐明肌成纤维细胞激活和疾病。(3)最后，一旦我们对正常的肌成纤维细胞进行了充分的鉴定和病变肺我们将开始阐明其分子机制对它们的扩散负有责任。最终，这些研究将提供为未来人类LAM组织的研究奠定了基础，这将是至关重要的在建立LAM细胞增殖与肿瘤发生发展之间的联系新疗法。