| Summary: | <p>Abstract</p> <p>Background</p> <p>Apoptosis is a critical process in endothelial cell (EC) biology and pathology, which has been extensively studied at protein level. Numerous gene expression studies of EC apoptosis have also been performed, however few attempts have been made to use gene expression data to identify the molecular relationships and master regulators that underlie EC apoptosis. Therefore, we sought to understand these relationships by generating a Bayesian gene regulatory network (GRN) model.</p> <p>Results</p> <p>ECs were induced to undergo apoptosis using serum withdrawal and followed over a time course in triplicate, using microarrays. When generating the GRN, this EC time course data was supplemented by a library of microarray data from EC treated with siRNAs targeting over 350 signalling molecules.</p> <p>The GRN model proposed <it>Vasohibin-1</it> (<it>VASH1</it>) as one of the candidate master-regulators of EC apoptosis with numerous downstream mRNAs. To evaluate the role played by <it>VASH1</it> in EC, we used siRNA to reduce the expression of <it>VASH1.</it> Of 10 mRNAs downstream of VASH1 in the GRN that were examined, 7 were significantly up- or down-regulated in the direction predicted by the GRN.Further supporting an important biological role of <it>VASH1</it> in EC, targeted reduction of <it>VASH1</it> mRNA abundance conferred resistance to serum withdrawal-induced EC death.</p> <p>Conclusion</p> <p>We have utilised Bayesian GRN modelling to identify a novel candidate master regulator of EC apoptosis. This study demonstrates how GRN technology can complement traditional methods to hypothesise the regulatory relationships that underlie important biological processes. </p>
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