Defining Apolipoprotein-mediated Regulatory Pathways in Asthmatic Airways

定义哮喘气道中载脂蛋白介导的调节途径

• 批准号: 9550553
• 负责人: Stewart Levine
• 金额: $ 16.88万
• 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/9550553
• 关键词: Apolipoprotein E; Apolipoproteins; Asthma; Candidate Disease Gene; Caring; Goals; Goblet Cells; Hyperplasia; Low Density Lipoprotein Receptor; Lung; Mediating; Mediator of activation protein; Mus; Pathogenesis; Pathway interactions; Pyroglyphidae; Regulatory Pathway; Respiratory physiology; Signal Pathway; Signal Transduction; airway hyperresponsiveness; asthmatic airway; experimental study; mouse model; novel

We have utilized a murine model of house dust mite-induced asthma to identify that an apolipoprotein E - low density lipoprotein (LDL) receptor pathway in the lung functions as an endogenous negative regulator of airway hyperreactivity and goblet cell hyperplasia (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). This identified a novel mechanism by which the pathogenesis of house dust mite-induced asthma is modulated. Ongoing experiments are utilizing mice with deletions of candidate genes in candidate apoE-LDLR signaling pathways to define further the mechanisms by which apoE-LDLR signaling negatively regulates airway hyperreactivity and goblet cell hyperplasia in asthma.

我们已经利用了肺部尘螨引起的鼠类尘埃菌诱导的鼠模型，以确定肺中的载脂蛋白E-低密度脂蛋白（LDL）受体途径是气道高反应性的内源性负调节剂，与go蛋白的增生剂（Apolipopropopoprotia e）相对于粉尘的粉尘弥漫，使粉质蛋白质e的粉质调节均与粉尘粉碎。 Yao X，Fredriksson K，Yu ZX，Xu X，Raghavachari N，Keeran KJ，Zywicke GJ，Kwak M，Amar MJ，Remaley，Remaley，Levine SJ。 这确定了一种新的机制，通过该机制调节房屋尘螨诱导的哮喘的发病机理。 正在进行的实验正在利用候选APOE-LDLR信号通路中删除候选基因的小鼠，以进一步定义APOE-LDLR信号通过哮喘中APOE-LDLR信号负调节气道高反应性和杯状细胞增生的机制。

项目成果

The A's Have It: Developing Apolipoprotein A-I Mimetic Peptides Into a Novel Treatment for Asthma.

A 拥有它：将载脂蛋白 A-I 模拟肽开发成治疗哮喘的新型疗法。

• DOI: 10.1016/j.chest.2016.05.035
• 发表时间: 2016
• 期刊: Chest
• 影响因子: 9.6
• 作者: Yao,Xianglan;Gordon,ElizabethM;Barochia,AmishaV;Remaley,AlanT;Levine,StewartJ
• 通讯作者: Levine,StewartJ

High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease.

• DOI: 10.3389/fphar.2016.00323
• 发表时间: 2016
• 期刊: Frontiers in pharmacology
• 影响因子: 5.6
• 作者: Gordon EM;Figueroa DM;Barochia AV;Yao X;Levine SJ
• 通讯作者: Levine SJ