Division of Natural Sciences, New College of Florida, Sarasota, FL, USA.
Department of Medicine, University of Pittsburgh, NW628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USA.
BMC Genomics. 2019 Jan 9;20(1):22. doi: 10.1186/s12864-018-5409-z.
Aging is affected by genetic and environmental factors, and cigarette smoking is strongly associated with accumulation of senescent cells. In this study, we wanted to identify genes that may potentially be beneficial for cell survival in response to cigarette smoke and thereby may contribute to development of cellular senescence.
Primary human bronchial epithelial cells from five healthy donors were cultured, treated with or without 1.5% cigarette smoke extract (CSE) for 24 h or were passaged into replicative senescence. Transcriptome changes were monitored using RNA-seq in CSE and non-CSE exposed cells and those passaged into replicative senescence. We found that, among 1534 genes differentially regulated during senescence and 599 after CSE exposure, 243 were altered in both conditions, representing strong enrichment. Pathways and gene sets overrepresented in both conditions belonged to cellular processes that regulate reactive oxygen species, proteasome degradation, and NF-κB signaling.
Our results offer insights into gene expression responses during cellular aging and cigarette smoke exposure, and identify potential molecular pathways that are altered by cigarette smoke and may also promote airway epithelial cell senescence.
衰老是受遗传和环境因素影响的，而吸烟与衰老细胞的积累密切相关。在这项研究中，我们希望确定可能对香烟烟雾有潜在生存益处的基因，从而可能有助于细胞衰老的发展。
培养了来自五位健康供体的原代人支气管上皮细胞，用或不用 1.5%香烟烟雾提取物（CSE）处理 24 小时或传代进入复制性衰老。使用 RNA-seq 在 CSE 和非 CSE 暴露的细胞以及传代进入复制性衰老的细胞中监测转录组变化。我们发现，在衰老过程中差异调节的 1534 个基因和 CSE 暴露后差异调节的 599 个基因中，有 243 个在两种情况下都发生了改变，这代表着强烈的富集。在两种情况下都过度表达的途径和基因集属于调节活性氧、蛋白酶体降解和 NF-κB 信号的细胞过程。
我们的研究结果提供了对细胞衰老和香烟烟雾暴露过程中基因表达反应的深入了解，并确定了可能被香烟烟雾改变并可能促进气道上皮细胞衰老的潜在分子途径。
