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。 由于它们在肺中的高能量功能和位置，它们高度依赖于线粒体。 电子烟设备产生的气雾剂含有颗粒和气相、尼古丁和香料。 香料成分和电子烟(电子烟)气雾剂对ATII细胞的影响尚不清楚。 线粒体dna(Mtdna)容易受到损伤，这是因为缺乏组蛋白来作为对抗 破坏性因素。线粒体DNA损伤可导致有丝分裂和ATII细胞死亡。我们的初步结果 展示带有水果和甜点味道的电子烟气雾剂对人和小鼠的有害影响 ATII细胞。DJ-1具有细胞保护作用，参与转录调控和线粒体功能。 我们的假设是，调味成分和带有水果和甜点味道的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 检测加味成分和电子烟气雾剂对人体线粒体功能的影响 ATII细胞。DJ-1在ATII细胞中的细胞保护作用机制将在SA#2中进行研究。在SA#3中，我们将 野生型和DJ-1 KO中加香成分和电子烟气雾剂的呼吸损伤风险分析 老鼠。目前的项目将填补我们在这种暴露对原代ATII细胞的影响方面的知识空白 和呼吸功能，并可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.