Thesis
TRANSCRIPTOMIC IDENTIFICATION OF GENES ASSOCIATED WITH THROMBOSIS AND COAGULATION IN LIPOPOLYSACCHARIDE-EXPOSED BOVINE MONOCYTE-DERIVED MACROPHAGES
Washington State University
Master of Science (MS), Washington State University
05/2024
DOI:
https://doi.org/10.7273/000006923
Abstract
Dysregulation of the inflammatory and hemostatic systems in patients with septicemia often leads to disorders of coagulation. Furthermore, septic patients who develop coagulation disorders frequently face higher mortality compared to those who do not. Thus, there is a critical need to better understand the processes that contribute to a procoagulant state in patients with septicemia, which may lead to the discovery of potential biomarkers to aid in the diagnosis of and prognostication of sepsis. This study used transcriptomics to characterize the differential expression of genes associated with coagulation in bovine-monocyte-derived macrophages (BMDMs) exposed to E. coli lipopolysaccharide (LPS) in vitro relative to a control. We hypothesized that there would be upregulation of procoagulant genes and downregulation of genes that protect against coagulation in BMDMs exposed to LPS relative to a control. We identified 1602 genes that were upregulated and 1209 genes that were downregulated three hours after exposure to LPS. BMDMs exposed to LPS displayed statistically significant upregulation of two pro-inflammatory genes (interleukin-6/IL6, tumor necrosis factor alpha/TNF-α), eight genes involved in promoting coagulation (P-selectin/SELP, tissue factor/F3, factor V/F5, factor XI/F11, plasminogen activator inhibitor 1/SERPINE1, plasminogen activator inhibitor 2/SERPINB2, vascular endothelial growth factor A/VEGFA, thrombospondin 1/THBS1), and five genes considered protective against coagulation (heparan sulfate-glucosamine 3 sulfotransferase 1/HS3ST1, prostaglandin I2 receptor/PTGIR, protein C receptor/PROCR, plasminogen activator urokinase receptor/PLAUR, and tissue factor pathway inhibitor 2/TFPI2). In addition, there was significant downregulation of one gene involved in the promotion of coagulation (thromboxane A2 receptor/TBXA2R). In summary, our data further support the link between inflammation and coagulation in BMDMs exposed to LPS and demonstrate the utility of using BMDMs as a model system to investigate sepsis-associated coagulopathies. These insights into the early transcriptomic changes in response to LPS may help guide future research on the development of treatment modalities or diagnostic tests for patients with sepsis.
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Details
- Title
- TRANSCRIPTOMIC IDENTIFICATION OF GENES ASSOCIATED WITH THROMBOSIS AND COAGULATION IN LIPOPOLYSACCHARIDE-EXPOSED BOVINE MONOCYTE-DERIVED MACROPHAGES
- Creators
- Hannah Rose Cohen
- Contributors
- Cleverson de Souza (Co-Chair)Jillian Haines (Co-Chair)William C. Davis (Committee Member)Mara S. Varvil (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- College of Veterinary Medicine
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 42
- Identifiers
- 99901125240601842
- Language
- English
- Resource Type
- Thesis