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

Garcia-Ryde, Martin LU (2024) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide according to 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 stress present in the lungs of COPD patients, such as smoking induced endoplasmic reticulum stress or hypoxic stress caused by pathological changes in the lung. Many of the mechanisms behind COPD are still unknown, such as why some people develop COPD while others do not despite similar smoking habits. We have investigated differences in how lung fibroblasts from healthy and COPD subjects react at the transcriptional level to cigarette smoke extract or... (More)
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide according to 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 stress present in the lungs of COPD patients, such as smoking induced endoplasmic reticulum stress or hypoxic stress caused by pathological changes in the lung. Many of the mechanisms behind COPD are still unknown, such as why some people develop COPD while others do not despite similar smoking habits. We have investigated differences in how lung fibroblasts from healthy and COPD subjects react at the transcriptional level to cigarette smoke extract or hypoxic exposure. We have also stained the cells to visualize and measure stress related proteins. Additionally, two epithelial cell lines of alveolar or bronchial origin were investigated in a similar way. From these investigations, we have found that there is a difference in how COPD subjects respond to stress, compared to healthy subjects. The healthy subjects go through several changes in expression to try to solve the stress, while this response is lacking in subjects with COPD. This difference is especially noticeable in pathways relating to apoptosis and cell proliferation, but also in pathways relating to hypoxic and endoplasmic reticulum stress. Lung fibroblasts from healthy subjects go into senescence in response to the stress and if the cell fails to resolve the stress, it undergoes apoptosis. Lung fibroblasts from COPD subjects on the other hand regulate different pathways and go straight into apoptosis. This atypical and deficient response in COPD subjects could be a contributing factor to disease progression and to why some people develop the disease. (Less)
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author
supervisor
opponent
  • Professor of Molecular Pharmacology Schmidt, Martina, University of Groningen, Faculty of Medical Sciences, Groningen, Netherlands
organization
publishing date
type
Thesis
publication status
published
subject
keywords
COPD, Cigarette smoke extract (CSE), Lung fibroblasts, Hypoxia, Gene expression
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2024:24
pages
67 pages
publisher
Lund University, Faculty of Medicine
defense location
Segerfalksalen, BMC A10, Sölvegatan 17 i Lund
defense date
2024-02-29 09:15:00
ISSN
1652-8220
ISBN
978-91-8021-517-6
language
English
LU publication?
yes
id
4cd176c1-b46c-4a23-9eb4-04411abbcce5
date added to LUP
2024-02-05 16:20:57
date last changed
2024-02-08 11:15:37
@phdthesis{4cd176c1-b46c-4a23-9eb4-04411abbcce5,
  abstract     = {{Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide according to 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 stress present in the lungs of COPD patients, such as smoking induced endoplasmic reticulum stress or hypoxic stress caused by pathological changes in the lung. Many of the mechanisms behind COPD are still unknown, such as why some people develop COPD while others do not despite similar smoking habits. We have investigated differences in how lung fibroblasts from healthy and COPD subjects react at the transcriptional level to cigarette smoke extract or hypoxic exposure. We have also stained the cells to visualize and measure stress related proteins. Additionally, two epithelial cell lines of alveolar or bronchial origin were investigated in a similar way. From these investigations, we have found that there is a difference in how COPD subjects respond to stress, compared to healthy subjects. The healthy subjects go through several changes in expression to try to solve the stress, while this response is lacking in subjects with COPD. This difference is especially noticeable in pathways relating to apoptosis and cell proliferation, but also in pathways relating to hypoxic and endoplasmic reticulum stress. Lung fibroblasts from healthy subjects go into senescence in response to the stress and if the cell fails to resolve the stress, it undergoes apoptosis. Lung fibroblasts from COPD subjects on the other hand regulate different pathways and go straight into apoptosis.  This atypical and deficient response in COPD subjects could be a contributing factor to disease progression and to why some people develop the disease.}},
  author       = {{Garcia-Ryde, Martin}},
  isbn         = {{978-91-8021-517-6}},
  issn         = {{1652-8220}},
  keywords     = {{COPD; Cigarette smoke extract (CSE); Lung fibroblasts; Hypoxia; Gene expression}},
  language     = {{eng}},
  number       = {{2024:24}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Stress Response in Chronic Obstructive Pulmonary Disease - Effect of Cigarette Smoke Extract and Hypoxia on Structural Lung Cells}},
  url          = {{https://lup.lub.lu.se/search/files/170815214/Avhandling_Martin_Ryde_utan_papers.pdf}},
  year         = {{2024}},
}