Lucile E. Wrenshall, M.D., Ph.D. (Advisor); Shulin Ju, Ph.D. (Committee Member); Paula Bubulya, Ph.D. (Committee Member)
Master of Science (MS)
Atherosclerosis is responsible for 50% of all deaths in western society and is the main cause of cardiovascular diseases (Pahwa et al. 2020). Vascular smooth muscle cells (VSMC) play a vital role in the development of atherosclerotic plaques; this is due to their ability to proliferate and migrate in response to inflammation and damage to arteries’ inner linings. To further understand what causes these cells to proliferate and migrate, our lab has previously found that VSMC express all three subunits of the IL-2 receptor (IL-2R). Out of these three subunits, IL-2Rα appeared to change the most depending on the phenotype of the cell. Our studies have shown that IL-2Rα could play a vital role in VSMC switching from a proliferative phenotype to a quiescent phenotype, in response to injury and inflammation. The present studies found that not only does the nuclear localization of IL-2Rα impact VSMC proliferation, but that commercially available knockout mice are not fully knocked out. In the first study, we utilized immunofluorescent staining, western blotting, and proliferation and migration assays to show that, when IL-2Rα localizes to the nucleus, VSMC proliferation is inhibited, therefore providing a possible means for regulation. In the second study, we used similar methodology in addition to PCR to show that IL-2Rα knock out mice are not completely devoid of IL-2Rα. Because the IL-2Rα knock out was generated using a neomycin resistance gene insert, we were able to eliminate the majority of IL-2Rα producing cells via treatment with G418, a neomycin analog. Treatment with G418 therefore allowed us to study VSMC nearly depleted of IL-2Rα. These findings are important in contributing to knowledge of the role of IL2-Rα in VSMC function, which could later aid in developing treatments for intimal hyperplasia and, in turn, atherosclerosis. In addition, knowing that the mice are only partially knocked out is beneficial to future investigators working with these mice.
Department or Program
Department of Biological Sciences
Year Degree Awarded
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