The transcription factor Miz1-mediated mechanisms of lung aging

转录因子Miz1介导的肺衰老机制

• 批准号: 9764468
• 负责人: JING LIU
• 金额: $ 4.69万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-19 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9764468
• 关键词: Age; Aging; Alveolar Macrophages; Animals; Cause of Death; Cell Aging; Cell Cycle; Cell Cycle Arrest; Cell Cycle Inhibition; Cells; Characteristics; Chronic; Chronic Obstructive Airway Disease; Chronic lung disease; Complex; Data; Development; Embryo; Epigenetic Process; Epithelial; Epithelial Cells; Gene Expression; Genes; Genetic; Growth Factor; HDAC1 gene; Human; Immunology; In Vitro; Inflammation; Inflammatory; Knockout Mice; Lead; Link; Lung; Mass Spectrum Analysis; Mediating; Molecular; Mus; Nature; Paper; Pathogenesis; Pathology; Pathway interactions; Patients; Peptide Hydrolases; Pharmaceutical Preparations; Phenotype; Production; Proteins; Pulmonary Emphysema; Pulmonary Inflammation; Reporter; Reporting; Repression; Risk Factors; Role; Tissues; Transcriptional Activation; Tumor Suppression; Zinc Fingers; age related; chemokine; chromatin remodeling; cytokine; differential expression; effective therapy; experimental study; genome wide association study; inhibitor/antagonist; insight; loss of function; normal aging; novel therapeutics; prevent; programs; recruit; senescence; therapeutic target; transcription factor; transcriptome sequencing

Project Summary/Abstract Chronic obstructive pulmonary disease (COPD) has risen to the third leading cause of death in the US and specific and effective therapies are not available. Age is the most important risk factor for COPD. The mechanisms of age-related changes that lead to COPD pathogenesis are poorly understood. In this proposal, we will study whether Miz1 epigenetically represses NF-B-dependent components of senescence-associated secretory phenotype (SASP), which acts in cooperation with inhibition of cell cycle arrest to suppress the senescence program, thereby preventing the development of COPD. Completion of this proposal, which includes animal and human studies, will provide fundamental insights into the pathogenesis of COPD and thus provide therapeutic targets.

项目摘要/摘要 慢性阻塞性肺疾病(COPD)已上升为美国第三大死因， 目前还没有特效的治疗方法。年龄是慢性阻塞性肺疾病最重要的危险因素。这个 导致COPD发病机制的年龄相关性变化的机制尚不清楚。在这份提案中， 我们将研究Miz1是否在表观遗传学上抑制衰老相关的NF-B依赖成分 分泌表型(SASP)，与抑制细胞周期停滞协同作用，抑制细胞周期 衰老计划，从而防止COPD的发展。完成本提案，其中包括 动物和人体研究，将提供对COPD发病机制的基本见解，从而提供 治疗靶点。