The transcription factor Miz1-mediated mechanism of lung aging

转录因子Miz1介导的肺衰老机制

• 批准号: 10198018
• 负责人: JING LIU
• 金额: $ 49.03万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198018
• 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; 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; genetic corepressor; genome wide association study; genomic locus; 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）已上升到美国的第三大死亡原因， 具体有效的疗法不可用。年龄是COPD的最重要危险因素。这 鲜为人知的导致COPD发病机理的年龄相关变化的机制知之甚少。在此提案中， 我们将研究MIZ1是否表观遗传反映了与衰老相关的NF-B依赖性成分 秘书表型（SASP），该表型与抑制细胞周期停滞合作以抑制 感应程序，从而阻止COPD的发展。该提案的完成，其中包括 动物和人类研究将提供对COPD发病机理的基本见解，从而提供 治疗靶标。

项目成果

Identification of the SARS-CoV-2 Entry Receptor ACE2 as a Direct Target for Transcriptional Repression by Miz1.

• DOI: 10.3389/fimmu.2021.648815
• 发表时间: 2021
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Yang J;Perez EA;Hou C;Zhang P;Van Scoyk M;Winn RA;Rong L;Liu J
• 通讯作者: Liu J

Dampening the Fire: A Negative Feedback Loop in Acute Respiratory Distress Syndrome.

• DOI: 10.1165/rcmb.2020-0487ed
• 发表时间: 2021-03
• 期刊: American journal of respiratory cell and molecular biology
• 影响因子: 6.4
• 作者: Liu J;Sala MA;Kim J
• 通讯作者: Kim J