An Investigation of Two Notch Regulated Genes in the Cardiovascular System
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Date
2018-05
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The Ohio State University
Abstract
The Notch signaling pathway is an important regulator of vascular development and physiology. Notch signaling operates via cell-to-cell contact, which manifests in the vasculature as ligands on endothelial cells interacting with receptors on smooth muscle cells to affect downstream signaling. In the current study, I demonstrate that coculture with endothelial cells induces the expression of Cytoglobin in smooth muscle cells. Cytoglobin is a widely expressed hexacoordinate hemoglobin protein implicated in maintaining cellular homeostasis. Further, I demonstrate that endothelial cell-derived expression of Cytoglobin in smooth muscle cells is dependent on the Notch signaling pathway and that Notch signaling is required for activation of Cytoglobin expression in cocultured smooth muscle cells. My studies also reveal a role for Cytoglobin in enabling smooth muscle cells to regulate nitric oxide bioavailability and to manage vascular derived stress. The second part of this study characterizes two lines of miR-145 transgenic mice referred to as the AA line and the DA line. MicroRNA miR-145 is a regulatory RNA that is influenced by Notch signaling and implicated in the progression of cardiac fibrosis. Although work is still in progress, the AA transgenic line demonstrates increased embryonic expression of mature miR-145 (relative to wild type) in mice expressing both RFP/ miR-145 and Myocd Cre. Additionally, two-week-old AA line pups demonstrate phenotypic abnormalities of the heart. Moving forward, the AA and DA lines will be further characterized and the effect that overexpression of miR-145 has on angiotensin II-induced cardiac fibrosis will be investigated.
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Keywords
Notch Signaling, Cytoglobin, miR-145, cardiac fibrosis