Molecular Control of Arterial Calcification
Matrix Gla Protein (MGP) is involved in the prevention of calcification of arteries, which is a process directly related to cardiovascular diseases. Transcriptional control of MGP is poorly understood, but evidence suggests that several signaling pathways and transcription factors (BMP, Notch, and Runx2) regulate MGP expression and this work examines these interactions. To accomplish this we cloned the MGP promoter into a luciferase reporter construct to enable convenient promoter analysis. Results thus far from two cell lines have shown that BMP increases MGP promoter activity while Notch decreases promoter activity. Evidence also exists showing that single nucleotide polymorphisms of the MGP promoter exist within the general population and a couple of these are correlated with a higher risk of cardiovascular disease. The second part of this work examines if these mutations effect the activation of the MGP promoter, and preliminary data shows that these mutations have varying effects on the activity. To give another perspective on this data we are incorporating RT-PCR and qPCR techniques which monitor endogenous promoter activity. Collectively, this data suggests that MGP expression is checked by a feedback loop involving Notch, BMP, and Runx2, and that promoter mutations vary MGP transcriptional activity.
Crow, Jacob, "Molecular Control of Arterial Calcification" (2015). College of Arts and Sciences Presentations. Paper 58.