Publication Date
2018
Document Type
Thesis
Committee Members
Ji Chen Bihl (Committee Member), Ravi Sahu (Committee Member), Jeffrey Travers (Advisor)
Degree Name
Master of Science (MS)
Abstract
Microvesicle particles (MVPs) are produced from cellular membranes and are thought to mediate cell-cell communication, including in response to stressors such as UVB radiation and thermal burn injury. Previous studies have shown that stress-induced MVP release requires the platelet-activating factor (PAF) receptor in human keratinocytes and that pharmacological inhibition of acid sphingomyelinase (ASM) blocked this release. To validate a genetic role for ASM in MVP release, we used CRISPR-Cas9 gene silencing in human keratinocytes and primary fibroblasts derived from ASM-knockout mice. Though MVP release was partially blocked in ASM-deficient mouse fibroblasts, the inability to fully knockdown ASM in HaCaT cells resulted in no significant impact on MVP production. We also found that ethanol, which is known to augment PAF production, stimulated MVP release in human keratinocytes and in mice in vivo. These studies therefore provide additional insights into the role of ASM and ethanol in MVP release.
Page Count
72
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
2018
Copyright
Copyright 2018, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
ORCID ID
0000-0002-0312-7635
