Publication Date
2023
Document Type
Thesis
Committee Members
Jeffrey B. Travers, M.D., Ph.D. (Advisor); David Cool, Ph.D. (Committee Member); Yangfang Chen, M.D., Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
The skin is exposed to a variety of external stressors, from irritants to toxic agents to ultraviolet radiation (UVR). While mice and human volunteers can be used for research studies, there are limitations in the range of environmental stressors that can be studied using these models. Therefore, our research team has been investigating the use of human skin explants as a model to study the immediate effects of environmental stressors ex vivo. Although this method has been successful, obtaining fresh human skin for these studies is difficult due to limited availability. To overcome this issue, we are evaluating the possibility of using porcine skin explants in our model systems. The primary advantage of using porcine skin is that it is readily available in large quantities, and its structure bears many similarities to that of human skin. In our research, we have found that various stressors, including UVB radiation, can trigger the production of Platelet-Activating Factor (PAF) in the skin. This, in turn, activates the enzyme acid sphingomyelinase (aSMase), leading to the shedding of subcellular microvesicle particles (MVP). In our research studies, we have used various models, such as cell lines, mice, human skin explants, and limited studies in human volunteers. Currently, we are examining the possibility of using porcine skin explants as a model to study MVP release in response to different types of stressors that are relevant to the skin. The application of the carbamyl PAF agonist PAF (CPAF) or a phorbol ester topically to the skin leads to an increase in MVP release. Similarly, exposing the skin to different UVB fluences also results in a higher release of MVP. Our experiments on porcine skin explants show similar results to human skin explants in terms of MVP release, although porcine skin appears to be less reactive to these agents. Although porcine skin shares many structural similarities with human skin, unlike human skin and cell lines, the combined impact of these stressors on porcine skin did not produce any synergistic results. Similar physiology does not necessarily imply that the skin will react to external stimuli in the same way. As the use of porcine skin in this type of skin model is relatively new, further research is needed to evaluate all parameters before considering porcine skin as a viable substitute for human skin models.
Page Count
55
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
2023
Copyright
Copyright 2023, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
ORCID ID
0009-0006-1188-697X
