Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders
(2023) In Frontiers in Physiology 14. p.1-13- Abstract
Introduction: Chronic lung disorders involve pathological alterations in the lung tissue with hypoxia as a consequence. Hypoxia may influence the release of inflammatory mediators and growth factors including vascular endothelial growth factor (VEGF) and prostaglandin (PG)E
2. The aim of this work was to investigate how hypoxia affects human lung epithelial cells in combination with profibrotic stimuli and its correlation to pathogenesis.
Methods: Human bronchial (BEAS-2B) and alveolar (hAELVi) epithelial cells were exposed to either hypoxia (1% O
2) or normoxia (21% O
2) during 24 h, with or without transforming growth factor (TGF)-β1. mRNA expression of genes and proteins related to disease pathology were... (More)
(Less)
Introduction: Chronic lung disorders involve pathological alterations in the lung tissue with hypoxia as a consequence. Hypoxia may influence the release of inflammatory mediators and growth factors including vascular endothelial growth factor (VEGF) and prostaglandin (PG)E
2. The aim of this work was to investigate how hypoxia affects human lung epithelial cells in combination with profibrotic stimuli and its correlation to pathogenesis.
Methods: Human bronchial (BEAS-2B) and alveolar (hAELVi) epithelial cells were exposed to either hypoxia (1% O
2) or normoxia (21% O
2) during 24 h, with or without transforming growth factor (TGF)-β1. mRNA expression of genes and proteins related to disease pathology were analysed with qPCR, ELISA or immunocytochemistry. Alterations in cell viability and metabolic activity were determined.
Results: In BEAS-2B and hAELVi, hypoxia significantly dowregulated genes related to fibrosis, mitochondrial stress, oxidative stress, apoptosis and inflammation whereas VEGF receptor 2 increased. Hypoxia increased the expression of Tenascin-C, whereas both hypoxia and TGF-β1 stimuli increased the release of VEGF, IL-6, IL-8 and MCP-1 in BEAS-2B. In hAELVi, hypoxia reduced the release of fibroblast growth factor, epidermal growth factor, PGE
2, IL-6 and IL-8, whereas TGF-β1 stimulus significantly increased the release of PGE
2 and IL-6. TGF-β1 stimulated BEAS-2B cells showed a decreased release of VEGF-A and IL-8, while TGF-β1 stimulated hAELVi cells showed a decreased release of PGE
2 and IL-8 during hypoxia compared to normoxia. Metabolic activity was significantly increased by hypoxia in both epithelial cell types.
Discussion: In conclusion, our data indicate that bronchial and alveolar epithelial cells respond differently to hypoxia and profibrotic stimuli. The bronchial epithelium appears more responsive to changes in oxygen levels and remodelling processes compared to the alveoli, suggesting that hypoxia may be a driver of pathogenesis in chronic lung disorders.
- author
- Berggren-Nylund, Rebecca ; Ryde, Martin LU ; Löfdahl, Anna LU ; Ibáñez-Fonseca, Arturo LU ; Kåredal, Monica LU ; Westergren-Thorsson, Gunilla LU ; Tufvesson, Ellen LU and Larsson-Callerfelt, Anna-Karin LU
- organization
-
- Lung physiology and biomarkers (research group)
- Lung Biology (research group)
- LU Profile Area: Light and Materials
- Genetic Occupational and Environmental Medicine (research group)
- NanoLund: Centre for Nanoscience
- LTH Profile Area: Nanoscience and Semiconductor Technology
- WCMM-Wallenberg Centre for Molecular Medicine
- eSSENCE: The e-Science Collaboration
- Lund University Bioimaging Center
- Tornblad Institute (research group)
- Neonatology (research group)
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Frontiers in Physiology
- volume
- 14
- article number
- 1094245
- pages
- 1 - 13
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85150891261
- pmid:36994416
- ISSN
- 1664-042X
- DOI
- 10.3389/fphys.2023.1094245
- language
- English
- LU publication?
- yes
- additional info
- Copyright © 2023 Berggren-Nylund, Ryde, Löfdahl, Ibáñez-Fonseca, Kåredal, Westergren-Thorsson, Tufvesson and Larsson-Callerfelt.
- id
- 01fe39c0-6b3f-40cd-a073-d9f7205d1a70
- date added to LUP
- 2023-04-09 14:05:05
- date last changed
- 2024-04-19 18:27:56
@article{01fe39c0-6b3f-40cd-a073-d9f7205d1a70, abstract = {{<p><br> Introduction: Chronic lung disorders involve pathological alterations in the lung tissue with hypoxia as a consequence. Hypoxia may influence the release of inflammatory mediators and growth factors including vascular endothelial growth factor (VEGF) and prostaglandin (PG)E<br> 2. The aim of this work was to investigate how hypoxia affects human lung epithelial cells in combination with profibrotic stimuli and its correlation to pathogenesis. <br> Methods: Human bronchial (BEAS-2B) and alveolar (hAELVi) epithelial cells were exposed to either hypoxia (1% O<br> 2) or normoxia (21% O<br> 2) during 24 h, with or without transforming growth factor (TGF)-β1. mRNA expression of genes and proteins related to disease pathology were analysed with qPCR, ELISA or immunocytochemistry. Alterations in cell viability and metabolic activity were determined.<br> Results: In BEAS-2B and hAELVi, hypoxia significantly dowregulated genes related to fibrosis, mitochondrial stress, oxidative stress, apoptosis and inflammation whereas VEGF receptor 2 increased. Hypoxia increased the expression of Tenascin-C, whereas both hypoxia and TGF-β1 stimuli increased the release of VEGF, IL-6, IL-8 and MCP-1 in BEAS-2B. In hAELVi, hypoxia reduced the release of fibroblast growth factor, epidermal growth factor, PGE<br> 2, IL-6 and IL-8, whereas TGF-β1 stimulus significantly increased the release of PGE<br> 2 and IL-6. TGF-β1 stimulated BEAS-2B cells showed a decreased release of VEGF-A and IL-8, while TGF-β1 stimulated hAELVi cells showed a decreased release of PGE<br> 2 and IL-8 during hypoxia compared to normoxia. Metabolic activity was significantly increased by hypoxia in both epithelial cell types. <br> Discussion: In conclusion, our data indicate that bronchial and alveolar epithelial cells respond differently to hypoxia and profibrotic stimuli. The bronchial epithelium appears more responsive to changes in oxygen levels and remodelling processes compared to the alveoli, suggesting that hypoxia may be a driver of pathogenesis in chronic lung disorders.<br> </p>}}, author = {{Berggren-Nylund, Rebecca and Ryde, Martin and Löfdahl, Anna and Ibáñez-Fonseca, Arturo and Kåredal, Monica and Westergren-Thorsson, Gunilla and Tufvesson, Ellen and Larsson-Callerfelt, Anna-Karin}}, issn = {{1664-042X}}, language = {{eng}}, pages = {{1--13}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Physiology}}, title = {{Effects of hypoxia on bronchial and alveolar epithelial cells linked to pathogenesis in chronic lung disorders}}, url = {{http://dx.doi.org/10.3389/fphys.2023.1094245}}, doi = {{10.3389/fphys.2023.1094245}}, volume = {{14}}, year = {{2023}}, }