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：
10475678
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/10475678
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 Persons 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 injured airway lung injury lung regeneration mitochondrial dysfunction new therapeutic target novel 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 II 型肺泡 (ATII) 细胞产生并分泌肺表面活性物质，并在损伤后恢复上皮。由于它们的能量需求功能和位于肺部的位置，它们高度依赖线粒体。电子烟装置产生的气溶胶含有颗粒物和气相、尼古丁和香料。调味成分和电子烟气雾剂对 ATII 细胞的影响尚不清楚。由于缺乏作为屏障的组蛋白，线粒体 DNA (mtDNA) 很容易受到损伤。破坏因素。 MtDNA 损伤可导致线粒体自噬和 ATII 细胞死亡。我们的初步结果证明带有水果和甜点口味的电子烟气雾剂对人类和小鼠原发性有害影响 ATII细胞。 DJ-1具有细胞保护作用并参与转录调节和线粒体功能。我们的假设是，带有水果和甜点口味的调味成分和电子烟气雾剂会导致 DJ-1 功能受损导致线粒体功能障碍，导致 ATII 细胞死亡。在 SA#1 中，我们将确定人类原发性调味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 DJ-1 在 ATII 细胞中的细胞保护功能机制。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道损伤风险老鼠。当前的项目将填补我们关于这种暴露对原代 ATII 细胞影响的知识空白和呼吸功能，可以为肺再生提供新的治疗靶点。