Chromosome 17q, allergic inflammation, and remodeling

染色体 17q、过敏性炎症和重塑

基本信息

批准号：
8661705
负责人：
DAVID H BROIDE
金额：
$ 38.75万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-15 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8661705
关键词：
17q 17q21 ADAM-8 Allergens Allergic inflammation Antibodies Asthma CXC Chemokines Ca(2+)-Transporting ATPase Cells Chromosomes Data Development Early Diagnosis Early Intervention Early identification Endoplasmic Reticulum Epithelial Epithelial Cells Epithelium Future Gelatinase B Genes Human IL8 gene IgE In Vitro Inflammation Inflammatory Interferons Investigation Label Length Ligase Link Lung Lung diseases Mediating Metalloproteases Modeling Mucous body substance Mus Mutant Strains Mice Nature Orosomucoid Outcome Pathogenesis Pathway interactions Physiological Play Population Heterogeneity Proteins PubMed Publications Publishing Reagent Research Personnel Rhinovirus Role Science Signal Transduction Pathway Testing Transfection Transgenic Mice Transgenic Organisms Viral Virus activating transcription factor airway epithelium airway inflammation airway remodeling base beta-Chemokines chemokine cytokine endonuclease eosinophilic inflammation genetic association genome wide association study high risk in vivo insight knock-down mRNA Transcript Degradation mouse model novel oligoadenylate prevent public health relevance repaired respiratory virus response transgene expression

项目摘要

DESCRIPTION (provided by applicant): Genome wide association studies have identified strong linkage between chromosome 17q21 and asthma. The focus of this proposal is on ORMDL-3, a protein localized to chromosome 17q21, which has been highly linked to asthma in several genome wide association studies. The investigation of the function of ORMDL-3 in the lung in asthma in this proposal will be enhanced by the development of unique reagents in the investigators lab (e.g. universal and cell specific ORMDL-3 transgenic and ORMDL-3 deficient mice; development of antibody to ORMDL to perform immunohistological). Based on our preliminary data we hypothesize that allergen induced ORMDL-3 expression regulates expression of multiple epithelial pathways (inflammation, remodeling, repair), as well as the ER ATF6 pathway which together play an important role in the pathogenesis of asthma. The studies proposed will use in vitro (knock down or over-expression of ORMDL-3 in lung cells) and in vivo studies (ORMDL-3 transgenic and ORMDL-3 deficient mice) to determine the role of ORMDL3 in the pathogenesis of allergen and rhinoviral induced asthma.

描述（由申请人提供）：全基因组关联研究已确定染色体 17q21 与哮喘之间存在密切联系。该提案的重点是 ORMDL-3，一种定位于染色体 17q21 的蛋白质，在多项全基因组关联研究中，该蛋白质与哮喘高度相关。本提案中 ORMDL-3 在哮喘肺部功能的研究将通过研究人员实验室开发独特的试剂得到加强（例如通用和细胞特异性 ORMDL-3 转基因和 ORMDL-3 缺陷小鼠；抗体的开发）到 ORMDL 进行免疫组织学）。根据我们的初步数据，我们假设过敏原诱导的 ORMDL-3 表达调节多种上皮途径（炎症、重塑、修复）以及 ER ATF6 途径的表达，这些途径共同在哮喘的发病机制中发挥重要作用。拟议的研究将使用体外（肺细胞中 ORMDL-3 的敲低或过度表达）和体内研究（ORMDL-3 转基因和 ORMDL-3 缺陷小鼠）来确定 ORMDL3 在过敏原和过敏原发病机制中的作用。鼻病毒诱发的哮喘。