RESPONSE IN LUNG EXTRACELLULAR MATRIX TO ASBESTOS

肺细胞外基质对石棉的反应

• 批准号: 7385766
• 负责人: Elizabeth A Putnam
• 金额: $ 14.08万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7385766
• 关键词: RESPONSE; LUNG; EXTRACELLULAR; MATRIX; ASBESTOS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Attention to asbestos-related diseases has re-emerged due to the exposure of Libby, Montana residents to asbestos-contaminated vermiculite. Vermiculite distribution to over 200 sites nationwide and the long latent period for disease development make asbestos-related diseases a continuing public health issue. Previous studies demonstrated increased expression of Sparc and Adam28 in asbestos-exposed mouse lungs, including those exposed to the Libby amphibole. Both Sparc and Adam 28 encode proteins involved in the regulation of extracellular matrix (ECM) ¿ cell interactions, including the tissue remodeling similar to that occurring during fibrosis. The functions of these proteins make them exciting candidates for involvement in the fibrosis that occurs after asbestos exposure. Our hypothesis is that expression of the proteins encoded by Sparc and Adam28 are significant steps in the development of lung fibrosis after asbestos exposure. To test the hypothesis, the specific aims will 1) establish the in vivo gene and protein expression of Sparc and Adam28 in Sparc-null and matched wild-type mice after exposure to saline, the Libby amphibole, and crocidolite asbestos and 2) determine the response of primary lung fibroblast cultures isolated from the Sparc-null and matched wild-type mice to the same three treatments by examining ECM production. The proposed studies will enhance understanding of the interaction between cells and ECM in response to the Libby amphibole. With health risks faced by thousands of exposed individuals, the ultimate goal of these studies is to identify novel therapeutic targets for these and other similar lung diseases.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一，该子项目和研究者 (PI) 可能已从其他 NIH 来源获得主要资助，因此可以在其他 CRISP 机构中得到体现。由于蒙大拿州利比居民接触受石棉污染的蛭石，石棉相关疾病再次受到关注。分布于全国 200 多个地点，并且疾病发展的潜伏期较长，使得石棉相关疾病成为一个持续的公共卫生问题。之前的研究增加了暴露于石棉的小鼠肺部（包括暴露于 Libby 角闪石的小鼠肺部）的 Sparc 和 Adam28 的表达。 Adam 28 编码参与细胞外基质 (ECM) 调节的蛋白质 ¿细胞相互作用，包括类似于纤维化过程中发生的组织重塑，这些蛋白质的功能使它们成为参与石棉暴露后发生的纤维化的令人兴奋的候选者，我们的假设是 Sparc 和 Adam28 编码的蛋白质的表达是重要的步骤。为了验证这一假设，具体目标是 1) 确定 Sparc 和 Adam28 在 Sparc 无效小鼠和匹配的野生型小鼠中的体内基因和蛋白表达。盐水、利比角闪石和青石棉，2) 通过检查 ECM 的产生，确定从 Sparc-null 和匹配的野生型小鼠中分离的原代肺成纤维细胞培养物对相同三种治疗的反应。由于数以千计的接触利比角闪石的个体面临着健康风险，这些研究的最终目标是确定这些疾病和其他类似肺部疾病的新治疗靶点。