权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Alveolar epithelial cell dysfunction induced by flavored e-cigarette aerosols

加香电子烟气雾剂引起的肺泡上皮细胞功能障碍

基本信息

批准号：
10046451
负责人：
Beata Kosmider
金额：
$ 35.61万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-10 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10046451
关键词：
Adenoviruses Aerosols Alveolar Cell Death Cell Differentiation process Cell physiology Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Chronic Computer Models DNA Damage Data Development Devices Electronic cigarette Epithelial Epithelial Cells Epithelium Exposure to Family Flavoring Food Fruit Functional disorder Gases Glycerol Goals Histones Human Impairment Ingestion Inhalation Injury Knockout Mice Knowledge Lead Location Lung Mitochondria Mitochondrial DNA Mus National Institute of Environmental Health Sciences Nicotine Nuclear Particulate Phase Production Propylene Glycols Publishing Pulmonary Emphysema Pulmonary Surfactants Reporting Respiration Respiratory physiology Risk Role Testing Time Toxic effect Transcriptional Regulation Vegetables Wild Type Mouse alveolar epithelium alveolar type II cell cell injury cigarette smoke e-cigarette aerosols electronic cigarette use electronic liquid improved lung injury lung regeneration mitochondrial dysfunction new therapeutic target novel respiratory response treatment strategy vaping

项目摘要

Abstract Alveolar type II (ATII) cells produce and secrete pulmonary surfactant and restore the epithelium after damage. Due to their energy-demanding functions and location in the lung, they are highly dependent on mitochondria. Aerosols produced from e-cigarette devices contain both the particulate and gas phases, nicotine and flavors. The effect of flavored constituents and electronic cigarette (e-cigarette) aerosols on ATII cells is unknown. Mitochondrial DNA (mtDNA) is susceptible to damage due to the lack of histones that serve as a barrier against damaging factors. MtDNA damage can lead to mitophagy and ATII cell death. Our preliminary results demonstrate the harmful effect of e-cigarette aerosols with fruit and dessert flavors on human and murine primary ATII cells. DJ-1 has a cytoprotective role and participates in transcriptional regulation and mitochondrial function. Our hypothesis is that flavored constituents and e-cigarette aerosols with fruit and dessert flavors cause mitochondrial dysfunction due to the impairment of DJ-1 function leading to ATII cell death. In SA#1, we will determine mitochondrial dysfunction induced by flavored constituents and e-cigarette aerosols in human primary ATII cells. The mechanism of DJ-1 cytoprotective function in ATII cells will be studied in SA#2. In SA#3, we will analyze the respiratory injury risk of flavored constituents and e-cigarette aerosols in wild-type and DJ-1 KO mice. The current project will fill the gap in our knowledge on the effect of this exposure on primary ATII cells and respiratory function and can provide novel therapeutic targets for lung regeneration.

摘要