Syndecan-1 Regulations of Influenza Infection

Syndecan-1 流感感染调控

• 批准号: 8812061
• 负责人: PETER CHEN
• 金额: $ 41.07万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8812061
• 关键词: Adult Respiratory Distress Syndrome; Antiviral Therapy; Apoptosis; Apoptotic; Appearance; Attenuated; Bacterial Infections; CD95 Antigens; Caspase Inhibitor; Cell membrane; Cell surface; Cessation of life; Communicable Diseases; Core Protein; Data; Dimethyl Sulfoxide; Disease; Disease Outbreaks; Epidemic; Epithelial; Event; Extracellular Domain; Immunity; Infection; Inflammatory; Influenza; Integration Host Factors; Lead; Lung; Lung Inflammation; Maps; Mediating; Mitochondria; Morbidity - disease rate; Mus; Pathway interactions; Patients; Proteoglycan; Proto-Oncogene Proteins c-akt; Receptor Signaling; Regulation; Respiratory Failure; Secondary to; Signal Transduction; TNFSF10 gene; Testing; Vaccine Production; Viral; Viral Drug Resistance; Viral Pneumonia; Virus Diseases; Wild Type Mouse; Work; airway epithelium; burden of illness; lung injury; mortality; mouse model; novel; novel therapeutics; pandemic disease; public health relevance; receptor; response; superinfection; syndecan

Project Summary/Abstract Influenza is a yearly epidemic that causes up to 500,000 global deaths annually. Most patients die of respiratory failure from either a primary viral pneumonia or a secondary bacterial infection. Therefore, finding host factors that can limit the progression of lung injury may lead to novel therapies for this deadly disease. Our preliminary data demonstrate that syndecan-1, a cell surface proteoglycan, regulates lung inflammation and reduces morbidity and mortality in mice after infection. Moreover, our data indicate that syndecan-1 restricts lung injury after influenza infection by limiting apoptosis in the airway epithelium. Our findings also show that syndecan-1 activates AKT, a pro-survival signal that can inhibit apoptosis. The central hypothesis for our proposal is that syndecan-1 is a pro-survival signal that attenuates epithelial apoptosis after influenza infection to limit lung injury. We will evaluate the mechanisms by which syndecan-1 regulates various apoptotic pathways. Additionally, we will investigate whether syndecan-1 suppresses apoptosis via activation of AKT. Finally, we will identify novel syndecan-1 co- receptors that mediate its cytoprotective effect. These studies will provide a platform for novel therapeutics that can target the airway epithelium to limit lung injury after influenza infection. This work may also have broader implications on other infectious diseases (viral and non-viral) of the lungs.

项目总结/文摘