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

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, ever‐smokers, 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 never‐smokers. 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.

Respiratory Function and Dysfunction in Parkinson-Type Neurodegeneration

“…The Golgi apparatus appears to be slightly smaller in the pulmonary fibroblasts of COPD patients (Golgi / nucleus ratio). This is in contrast to neurodegeneration where this organelle is fragmented and dispersed throughout the cell (Weidner et al 2018).…”

“…In favor of the similarity of COPD to neurodegeneration, data provided from mitochondrial research confirm disruption of fission/fusion processes and higher levels of ROS production by damaged mitochondria (Boukhenouna et al 2018). In a study by Weidner et al (2018), the morphology of endoplasmic reticulum in patients with COPD was also found to be altered in comparison to healthy subjects. Conversely, not so high degree of similarity was observed with other organelles.…”

Heme oxygenase-1(HO-1) regulates Golgi stress and attenuates endotoxin-induced acute lung injury through hypoxia inducible factor-1α (HIF-1α)/HO-1 signaling pathway

“…However, the mechanism of Golgi stress in the development of some lung diseases remain poorly understood. Weidner J, et al reported that there were disruption among endoplasmic reticulum(ER), Golgi, and lysosomes in fibroblasts from COPD patients[ 55 ].And they found the size of Golgi decreased in COPD patients, but the reason for this change is still not so clear[ 55 ]. GOLPH3(also named GMx33 and GPP34), a peripheral membrane protein, is localized to the trans-Golgi and extract vesicles from the Golgi [ 56 ].…”

<p>Human Lung Macrophages Challenged to Oxidants ex vivo: Lysosomal Membrane Sensitization is Associated with Inflammation and Chronic Airflow Limitation</p>

“…3,4 Another study of fibroblasts, harvested from the airways of subjects with COPD and healthy control subjects, showed that the endoplasmic reticulum, Golgi, and lysosomes were permanently disorganized in fibroblasts from COPD patients, and, moreover, in culture, these fibroblasts demonstrated increased vulnerability to cellular stress. 5 Oxidants probably play an important role for COPD development due to damage on single cells and tissues. 6 Such damage is possibly potentiated by a disturbed metabolism of iron.…”