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Embargoed until 2016-04-30
Copyright: An, Siwei
Embargoed until 2016-04-30
Copyright: An, Siwei
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Abstract
Background. Cardiovascular disease is a major cause of death and disability and
treatment options are limited. Abnormal vascular smooth muscle cell (VSMC)
proliferation is a key pathological feature in atherosclerosis, hypertension, and
stenosis and restenosis. In order to design new and effective strategies to cure or
prevent cardiovascular disease, it is important to better understand mechanisms of
gene transcription, mRNA translation and related signaling pathways.
Objective. The aims of this thesis were (i) to understand the function of YrdC in
translational control in VSMC, and (ii) to dissect the signal transduction pathways
underlying IL-1β-induced Egr-1 expression via MEK in VSMC.
Results. In the first study, YrdC, which is upregulated after VSMC injury, was found
to play a role in translational regulation, i.e. YrdC positively regulates protein
synthesis. In the second study, the involvement of EGFR (tyrosine 845
phosphorylation) in IL-1β-induced Egr-1 expression was demonstrated in both
VSMCs and mouse embryonic fibroblasts (MEF) and to mediate IL-1β-induced
VSMC migration and proliferation.
Conclusion. YrdC, once induced, may play a key role in promoting cell migration or
proliferation by mediating protein synthesis in the reparative response to injury in
VSMCs. IL-1β-induced Egr-1 expression is mediated through EGFR in VSMCs. These
findings provide important insights on signaling responses to vascular cell injury.