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.

我们已经利用了屋尘螨诱导的哮喘的鼠模型来鉴定肺中的载脂蛋白E -低密度脂蛋白（LDL）受体途径作为气道高反应性和杯状细胞增生的内源性负调节剂起作用（载脂蛋白E通过LDL受体介导的途径负调节屋尘螨诱导的哮喘。 Yao X，Fredriksson K，Yu ZX，Xu X，Raghavachari N，Keiden KJ，Zywicke GJ，Kwak M，Amar MJ，Remaley AT，Levine SJ. Am J Respir Crit Care Med. 2010年7月9日。Epub before print）。 这确定了一种新的机制，其中屋尘螨诱导的哮喘的发病机制是调制。 正在进行的实验利用候选apoE-LDLR信号通路中候选基因缺失的小鼠进一步确定apoE-LDLR信号负调节哮喘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