Endoplasmic reticulum, Golgi, and lysosomes are disorganized in lung fibroblasts from chronic obstructive pulmonary disease patients

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Abstract

Chronic Obstructive Pulmonary Disease (COPD) is often caused by smoking and other stressors. This causes oxidative stress, which induces numerous changes on both the transcriptome and proteome of the cell. We aimed to examine if the endomembrane pathway, including the endoplasmic reticulum (ER), Golgi, and lysosomes, was disrupted in fibroblasts from COPD patients as opposed to healthy ever-smokers or never-smokers, and if the response to stress differed. Different cellular compartments involved in the endomembrane pathway, as well as mRNA expression and apoptosis, were examined before and after the addition of stress in lung fibroblasts from never-smokers, eversmokers, and patients with COPD. We found that the ER, Golgi, and lysosomes were disorganized in fibroblasts from COPD patients under baseline conditions. After a time course with ER stress inducing chemicals, changes to the phenotypes of cellular compartments in COPD patient fibroblasts were observed, and the expression of the ER stress-induced gene ERP72 was upregulated more in the COPD patient’s cells compared to ever-smokers or neversmokers. Lastly, a tendency of increased active Caspase-3 was observed in COPD fibroblasts. Our results show that COPD patients have phenotypic changes in the lung fibroblasts endomembrane pathway, and respond differently to stress. Furthermore, these fibroblasts were cultured for several weeks outside the body, but they were not able to regain proper ER structure, indicating that the internal changes to the endomembrane system are permanent in smokers. This vulnerability to cellular stress might be a cause as to why some smokers develop COPD.

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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Respiratory Medicine and Allergy

Keywords

  • Chronic obstructive pulmonary disease, Endoplasmic reticulum, Endoplasmic reticulum stress response, Golgi, Lung fibroblast
Original languageEnglish
Article numbere13584
JournalPhysiological Reports
Volume6
Issue number5
Publication statusPublished - 2018 Mar 1
Publication categoryResearch
Peer-reviewedYes