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：
10259708
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/10259708
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 Exposure to Family Flavoring Food Fruit Functional disorder Gases 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 PARK7 gene Particulate Phase Production Propylene Glycols Publishing Pulmonary Emphysema Pulmonary Surfactants Reporting Respiration Respiratory physiology Risk Role Testing Time Toxic effect Transcriptional Regulation 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 vegetable glycerin

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.

抽象的肺泡II型（ATII）细胞产生并分泌肺表面活性剂，并在损伤后恢复上皮。由于它们的能量要求功能和肺部的位置，因此高度依赖于线粒体。电子烟设备产生的气溶胶既包含颗粒和气相，尼古丁和风味。风味成分和电子烟（电子烟）气溶胶对ATII细胞的影响尚不清楚。线粒体DNA（mtDNA）因缺乏作为屏障的组蛋白而易受损害有害因素。 mtDNA损伤会导致线粒体和ATII细胞死亡。我们的初步结果展示带有水果和甜点口味的电子烟气溶胶对人和鼠类主要的有害作用 atii细胞。 DJ-1具有细胞保护作用，并参与转录调控和线粒体功能。我们的假设是，带有水果和甜点风味的调味成分和电子烟气雾剂会导致线粒体功能障碍由于DJ-1功能受损导致ATII细胞死亡。在SA＃1中，我们将确定由人类原代成分和电子烟气溶胶引起的线粒体功能障碍 atii细胞。 SA＃2将研究ATII细胞中DJ-1细胞保护功能的机制。在SA＃3中，我们将分析野生型和DJ-1 KO中调味成分和电子烟气溶胶的呼吸损伤风险老鼠。当前项目将填补我们对这种暴露对主要ATII细胞影响的知识的空白和呼吸功能，可以为肺部再生提供新颖的治疗靶标。