RNA sequencing identifies common pathways between cigarette smoke exposure and replicative senescence in human airway epithelia

Abstract

BackgroundAging 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.ResultsPrimary 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5409-z) contains supplementary material, which is available to authorized users.

Systems approaches to investigate the role of NF-κB signaling in aging

“…Transcriptome changes in senescent cells induced by RS and cigarette smoke exposure also indicate that NF-κB is related to aging [ 93 ]. Cigarette smoke exposure and RS are well-known senescence inducers [ 94 ].…”

“…Cigarette smoke exposure and RS are well-known senescence inducers [ 94 ]. Voic et al [ 93 ] performed RNA-seq in passaged cigarette smoke extract (CSE)-exposed and non-CSE-exposed senescent primary human bronchial epithelial cells and showed that GSEA indicated dysfunction in the regulation of ROS, proteasome degradation, and NF-κB signaling under either RS or CSE. miRNA analysis has also been conducted to explore the influence of aging.…”

Senescence: Pathogenic Driver in Chronic Obstructive Pulmonary Disease

“…• * ROS signaling [26,39,40] • * NFκB signaling [47] • * p21 pathway [16,[28][29][30] • * Endoplasmic reticulum (ER) stress [48] • * SA-βgal activity [24,26,[35][36][37][38] Therapy-induced senescence * AREG, * CXCL8, * IL1A, * IL-1B, * IL-6, * IL8 * MMP2, * MMP3, * PAI-1, * SPINK1, * t-PA, and WNT16B…”

“…A recent study utilizing RNA sequencing approaches in CSE exposure and senescent conditions in airway epithelial cells demonstrated that CS and senescence conditions induce common signaling responses, including genes that regulate ROS, proteasome degradation, and NF-κB signaling [47]. Voic and colleagues report 243 common gene expression changes in epithelial cells when exposed to CSE or induced senescence [47].…”

“…A recent study utilizing RNA sequencing approaches in CSE exposure and senescent conditions in airway epithelial cells demonstrated that CS and senescence conditions induce common signaling responses, including genes that regulate ROS, proteasome degradation, and NF-κB signaling [47]. Voic and colleagues report 243 common gene expression changes in epithelial cells when exposed to CSE or induced senescence [47]. Several of these genes are already reported to play significant roles in COPD pathogenesis, such as MMP-1 [81] and S100A9 [42], suggesting shared changes induced by CSE and senescence in the pathogenesis of COPD.…”