title: Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.The GRN model proposed Vasohibin-1 (VASH1) as one of the candidate master-regulators of EC apoptosis with numerous downstream mRNAs. To evaluate the role played by VASH1 in EC, we used siRNA to reduce the expression of VASH1. 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 VASH1 in EC, targeted reduction of VASH1 mRNA abundance conferred resistance to serum withdrawal-induced EC death.
  
  
  CONCLUSIONS
  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.
authors: Department of Obstetrics and Gynaecology, University of Cambridge, The Rosie Hospital, Robinson Way, Cambridge CB2 0SW, UK.
authors: Muna
authors: M
authors: Affara
authors: Debbie
authors: D
authors: Sanders
authors: Hiromitsu
authors: H
authors: Araki
authors: Yoshinori
authors: Y
authors: Tamada
authors: Benjamin J
authors: BJ
authors: Dunmore
authors: Sally
authors: S
authors: Humphreys
authors: Seiya
authors: S
authors: Imoto
authors: Christopher
authors: C
authors: Savoie
authors: Satoru
authors: S
authors: Miyano
authors: Satoru
authors: S
authors: Kuhara
authors: David
authors: D
authors: Jeffries
authors: Cristin
authors: C
authors: Print
authors: D Stephen
authors: DS
authors: Charnock-Jones
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001499:Bayes Theorem; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D019295:Computational Biology; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C493181:VASH1 protein, human