Characterizing the Role of Apolipoprotein Receptors in Asthma Pathogenesis

表征载脂蛋白受体在哮喘发病机制中的作用

• 批准号: 8149567
• 负责人: Stewart Levine
• 金额: $ 15.03万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149567
• 关键词: Apolipoproteins; Asthma; Binding; Caring; Development; Epithelial Cells; Goals; Hyperplasia; Knockout Mice; Low Density Lipoprotein Receptor; Lung; Pathogenesis; Pathway interactions; Pharmaceutical Preparations; Printing; Role; insight; macrophage; receptor

We have identified that apolipoprotein E serves as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia in asthma by a low density lipoprotein receptor(LDLR)-dependent mechanism (Apolipoprotein E Negatively Regulates House Dust Mite-induced Asthma via a LDL Receptor-mediated Pathway. Yao X, Fredriksson K, Yu ZX, Xu X, Raghavachari N, Keeran KJ, Zywicke GJ, Kwak M, Amar MJ, Remaley AT, Levine SJ. Am J Respir Crit Care Med. 2010 Jul 9. Epub ahead of print). The effects of apoE, which is synthesized by macrophages in the lung, are mediated via binding to LDLRs that are expressed on ciliated airway epithelial cells. This project will utilize apolipoprotein receptor knock-out mice to define the role of other apolipoprotein receptors in modulating the pathogenesis of asthma. Furthermore, the mechanisms by which asthma pathogenesis is modulated by lung apolipoprotein receptors will be characterized.

我们已经确定，通过低密度脂蛋白受体（LDLR）依赖性机制，载脂蛋白E是气道高反应性和杯状细胞增生的内源性负调节剂（载脂蛋白E负调节house ducks house duck诱导的lddl rik rik siD rik iDied sidied sidied sidied sidied sidied sidied sidied rik sidied sidied ya a a y a a ya a a a y a a ya a a ya a a a a a a a a a ya a a a a y a a ya a。 Yu ZX，Xu X，Raghavachari N，Keeran KJ，Zywicke GJ，Kwak M，Amar MJ，Remaley，Levine SJ。 APOE的作用是由肺中巨噬细胞合成的，是通过与在纤毛气道上皮细胞上表达的LDLR结合介导的。 该项目将利用载脂蛋白受体敲除小鼠来定义其他载脂蛋白受体在调节哮喘发病机理中的作用。 此外，将表征哮喘发病机理调节哮喘发病机理的机制。