title: Polynomial algebra reveals diverging roles of the unfolded protein response in endothelial cells during ischemia-reperfusion injury.
abstract: The unfolded protein response (UPR)--the endoplasmic reticulum stress response--is found in various pathologies including ischemia-reperfusion injury (IRI). However, its role during IRI is still unclear. Here, by combining two different bioinformatical methods--a method based on ordinary differential equations (Time Series Network Inference) and an algebraic method (probabilistic polynomial dynamical systems)--we identified the IRE1α-XBP1 and the ATF6 pathways as the main UPR effectors involved in cell's adaptation to IRI. We validated these findings experimentally by assessing the impact of their knock-out and knock-down on cell survival during IRI.
authors.affiliation: IRTOMIT, INSERM UMR 1082, Université de Médecine et de Pharmacie de Poitiers, Rue de la Milétrie, 86021 Poitiers, France. Electronic address: sylvain.le.pape@univ-poitiers.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Le Pape
authors.affiliation: Mathematical Sciences, Clemson University, Martin O-303, Clemson, SC 29634-0975, United States.
authors.forename: Elena
authors.initials: E
authors.lastname: Dimitrova
authors.affiliation: IRTOMIT, INSERM UMR 1082, Université de Médecine et de Pharmacie de Poitiers, Rue de la Milétrie, 86021 Poitiers, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Hannaert
authors.affiliation: Centre for Interdisciplinary Research in Computational Algebra, School of Computer Science, University of St Andrews, St Andrews, Fife KY16 9SX, Scotland, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Konovalov
authors.affiliation: University of Cambridge Metabolic Research Laboratories and National Institute for Health Research, Cambridge Biomedical Research Centre, CB2 0QQ Cambridge, United Kingdom.
authors.forename: Romain
authors.initials: R
authors.lastname: Volmer
authors.affiliation: University of Cambridge Metabolic Research Laboratories and National Institute for Health Research, Cambridge Biomedical Research Centre, CB2 0QQ Cambridge, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Ron
authors.affiliation: IRTOMIT, INSERM UMR 1082, Université de Médecine et de Pharmacie de Poitiers, Rue de la Milétrie, 86021 Poitiers, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Thuillier
authors.affiliation: IRTOMIT, INSERM UMR 1082, Université de Médecine et de Pharmacie de Poitiers, Rue de la Milétrie, 86021 Poitiers, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Hauet
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D019295:Computational Biology / Q000379:methods*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004722:Endoribonucleases / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D015427:Reperfusion Injury / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D056811:Unfolded Protein Response; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases
keywords: Endothelial cells (EC); Gene regulatory networks (GRN); Ischemia–reperfusion injury (IRI); Murine embryonic cells (MEC); Probabilistic polynomial dynamical systems (PDS); Unfolded protein response (UPR)