Alveolar epithelial cell dysfunction induced by flavored e-cigarette aerosols

摘要 肺泡II型（ATII）细胞产生和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在肺中的位置，它们高度依赖于线粒体。 电子烟装置产生的气溶胶含有颗粒和气相、尼古丁和香料。 调味成分和电子烟（e-cigarette）气溶胶对ATII细胞的影响尚不清楚。 线粒体DNA（mtDNA）由于缺乏组蛋白而易受损伤，组蛋白作为抵抗线粒体DNA损伤的屏障。 破坏因素。线粒体DNA损伤可导致线粒体自噬和ATII细胞死亡。我们的初步结果 证明了具有水果和甜点口味的电子烟气溶胶对人类和小鼠的主要 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，风味成分和电子烟气溶胶与水果和甜点口味的原因 由于DJ-1功能受损导致的线粒体功能障碍导致ATII细胞死亡。在SA#1中，我们将 确定人类原发性癌症中调味成分和电子烟气溶胶诱导的线粒体功能障碍 ATII细胞。将在SA#2中研究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 小鼠目前的项目将填补差距，在我们的知识的影响，这种曝光对原代ATII细胞 和呼吸功能，为肺再生提供新的治疗靶点。

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.