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Stress Response in Chronic Obstructive Pulmonary Disease – Effect of Cigarette Smoke Extract and Hypoxia on Structural Lung Cells

Authors: Garcia-Ryde, Martin

Journal: Doctoral thesis (2024)

Institution: Lund Univerisity

Summary: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide accordingto the world health organization. It is a disease characterized by chronic inflammation and emphysema,and cigarette smoking is the main cause of COPD development. There are several forms of stresspresent in the lungs of COPD patients, such as smoking induced endoplasmic reticulum stress orhypoxic stress caused by pathological changes in the lung. Many of the mechanisms behind COPD arestill unknown, such as why some people develop COPD while others do not despite similar smokinghabits. We have investigated differences in how lung fibroblasts from healthy and COPD subjects reactat the transcriptional level to cigarette smoke extract or hypoxic exposure. We have also stained thecells to visualize and measure stress related proteins. Additionally, two epithelial cell lines of alveolar orbronchial origin were investigated in a similar way. From these investigations, we have found that thereis a difference in how COPD subjects respond to stress, compared to healthy subjects. The healthysubjects go through several changes in expression to try to solve the stress, while this response islacking in subjects with COPD. This difference is especially noticeable in pathways relating toapoptosis and cell proliferation, but also in pathways relating to hypoxic and endoplasmic reticulumstress. Lung fibroblasts from healthy subjects go into senescence in response to the stress and if thecell fails to resolve the stress, it undergoes apoptosis. Lung fibroblasts from COPD subjects on theother hand regulate different pathways and go straight into apoptosis. This atypical and deficientresponse in COPD subjects could be a contributing factor to disease progression and to why somepeople develop the disease.

Keywords: COPD, Cigarette smoke, hypoxia, gene expression, lung, fibroblast, epithel

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