Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

Bačura, Anita Somborac; Rumora, Lada; Novak, Ruđer; Rašić, Dubravka; Dumić, Jerka; Čepelak, Ivana; Žanić‐Grubišić, Tihana

doi:10.1113/ep087038

Cited by 19 publications

(11 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, when cells are damaged beyond repair, the UPR promotes elimination of afflicted cells through apoptosis [61]. Previous studies have also reported an increase in the expression of heat shock proteins in the alveolar epithelial cells exposed to cigarette smoke extract [62]. TCTP, a pro-survival molecule, has also been shown to play an important role in the UPR where it protects cells from the apoptotic cell death [61].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Smoking induces sex-specific changes in the small airway proteome

et al. 2021

View full text Add to dashboard Cite

Introduction Cigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking. Methods Exhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed. Results Two hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p < 0.05, q < 0.124). Among the proteins most clearly discriminating between current and never smokers were sRAGE, FSTL3, SPOCK2 and protein S, all of them being less abundant in current smokers. Analysis stratified for sex unveiled sex differences with more pronounced proteomic alterations due to active smoking in females than males. Proteins whose abundance was altered by active smoking in women were to a larger extent related to the complement system. The small airway protein profile of former smokers appeared to be more similar to that observed in never smokers. Conclusions The study shows that smoking has a strong impact on protein expression in the small airways, and that smoking affects men and women differently, suggesting PExA sampling combined with high sensitivity protein analysis offers a promising platform for early detection of COPD and identification of novel COPD drug targets.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The expression of heat shock proteins is increased in the alveolar epithelial cells exposed to cigarette smoke extract [62] (P08238)…”

Section: B2mmentioning

confidence: 99%

Smoking induces sex-specific changes in the small airway proteome

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Nevertheless, there were probably hundreds of miRNAs that are upregulated or downregulated in COPD (Ezzie et al, 2012;Osei et al, 2015;Sato et al, 2015;Szymczak et al, 2016;Conickx et al, 2017;Keller et al, 2018), and the aim of the present study was only to examine those that could modulate the CCL3/CCR5 axis. In addition, although A549 cells were used to study alveolar epithelial cells (Akram et al, 2013;Mortaz et al, 2017;Somborac-Bacura et al, 2018), they were malignant cells that might not reflect reality. Future studies should be done to examine a wide panel of miRNAs, and also to deline at the effects of circulating miRNAs vs. those of miRNAs produced locally in the lungs.…”

Section: Discussionmentioning

confidence: 99%

miR-4456/CCL3/CCR5 Pathway in the Pathogenesis of Tight Junction Impairment in Chronic Obstructive Pulmonary Disease

Ding

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Cigarette smoke exposure (CSE) is a major cause of chronic obstructive pulmonary disease (COPD). The smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the tight junction (TJ) proteins. Even though the inflammatory mechanism of chemokine (C-C motif) ligand 3 (CCL3) in COPD has gained increasing attention in the research community, however, the underlying signaling pathway, remains unknown.Objectives: To identify the relationship of CCL3 in the pathogenesis of tight junction impairment in COPD and the pathway through which CSE causes damage to TJ in COPD via CCL3, both in vivo and in vitro.Methods: We screened the inflammatory factors in the peripheral blood mononuclear cells (PBMCs) from healthy controls and patients at each GOLD 1-4 stage of chronic obstructive pulmonary disease. RT-PCR, western blot, and ELISA were used to detect the levels of CCL3, ZO-1, and occludin after Cigarette smoke exposure. Immunofluorescence was applied to examine the impairment of the TJs in 16-HBE and A549 cells. The reverse assay was used to detect the effect of a CCR5 antagonist (DAPTA) in COPD. In the CSE-induced COPD mouse model, H&E staining and lung function tests were used to evaluate the pathological and physical states in each group. Immunofluorescence was used to assess the impairment of TJs in each group. ELISA and RT-PCR were used to examine the mRNA or protein expression of CCL3 or miR-4456 in each group.Results: The in vivo and in vitro results showed that CCL3 expression was increased in COPD compared with healthy controls. CCL3 caused significant injury to TJs through its C-C chemokine receptor type 5 (CCR5), while miR-4456 could suppress the effect of CCL3 on TJs by binding to the 3′-UTR of CCL3.Conclusion: miR-4456/CCL3/CCR5 pathway may be a potential target pathway for the treatment of COPD.

show abstract

“…After 6 hr, the expression of HSP70 and HSP32 will be increased by CSE induce. And fortunately, all detected HSPs are upregulated after 8 hr and continuously increased to 48 hr (Somborac‐Bačura et al., 2018). Smoke and some other polluting gases were easily breathed in goats during the transport period.…”

Section: Discussionmentioning

confidence: 99%

Effects of transport stress on pathological injury and main heat shock protein expression in the respiratory system of goats

Zheng

Liu

et al. 2020

Animal Physiology Nutrition

View full text Add to dashboard Cite

The aim of the present study was to investigate the pathological injury and the expression of heat shock proteins in the caprine lung, trachea and bronchus under transport stress. 12 healthy male goats were selected and randomly divided into three groups. The control group (non‐transported group), 2 hr transport‐treated group and 6 hr transport‐treated group. Morphological changes as well as the expression of heat shock proteins (HSPs, mainly HSP27, HSP70 and HSP90) in three parts of the respiratory tract were examined. Our results showed swollen mucosa and congestive blood vessels in mucous layer and submucosa, inflammatory cell infiltration as well as degeneration and necrosis of mucosal epithelial cells in trachea and bronchus of the transport‐treated groups. The epithelial cells were degenerated, and the exfoliated cells and debris could be seen in the alveolar cavity. The results of immunohistochemistry showed that HSP27 and HSP70 were strongly expressed in tracheal and bronchial epithelium, glandular epithelium, vascular endothelium and bronchiole epithelium. And the amount of positive inflammatory cells was increased in transport‐treated groups. Western blot results indicated that the expression of all three proteins had no obvious difference among the three groups in bronchi (p > .05). In trachea, there was no significant difference in the expression of heat shock proteins among the three groups except that the expression of HSP70 which was obviously higher in the two transported groups than the control group (p < .05). The expression level of HSP70 in the 2 hr transport‐treated group was significantly higher than the 6 hr group (p < .05) and control groups (p < .05). However, there was no significant difference in the expression level of HSP27 and HSP90 in three groups (p > .05). In conclusion, our data showed that transport stress could damage the caprine respiratory system.

show abstract

Differential expression of heat shock proteins and activation of mitogen‐activated protein kinases in A549 alveolar epithelial cells exposed to cigarette smoke extract

Cited by 19 publications

References 72 publications

Smoking induces sex-specific changes in the small airway proteome

Smoking induces sex-specific changes in the small airway proteome

miR-4456/CCL3/CCR5 Pathway in the Pathogenesis of Tight Junction Impairment in Chronic Obstructive Pulmonary Disease

Effects of transport stress on pathological injury and main heat shock protein expression in the respiratory system of goats

Contact Info

Product

Resources

About