Comparison of the central human and mouse platelet signaling cascade by systems biological analysis
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RESEARCH ARTICLE
Open Access
Comparison of the central human and mouse platelet signaling cascade by systems biological analysis Johannes Balkenhol1, Kristin V. Kaltdorf1, Elmina Mammadova-Bach2,3, Attila Braun4, Bernhard Nieswandt2, Marcus Dittrich1,5 and Thomas Dandekar1*
Abstract Background: Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). Results: The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. Conclusions: Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences. Keywords: Interspecies comparison, Transcriptome, Proteome, Platelet, Network, Signaling, Mouse, Human, Interactome, Cascade
Summary The signal network of the central regulatory cascade in platelets was reconstructed. Transcriptomics and proteomics data of specific expression differences between human and mouse platelets were compared for this central cascade. * Correspondence: [email protected] 1 Functional Genomics and Systems Biology Group, Department of Bioinformatics, Biocenter, Am Hubland, University of Würzburg, D-97074 Würzburg, Germany Full list of author information is available at the end of the article
Background Blood platelets are anucleated small cells released from megakaryocytes (MKs) of the bone marrow into the blood. Circulating platelets adhere and aggregate at sites of vascular injury and together with the coagulation system form a fibrin rich clot to arrest bleeding [1]. On the other hand, platelets can cause pathological thrombosis and vessel occlusion leading to the most common lifethreating pathologies, myocardial infarction and stroke [2, 3] and are involved in many other (patho)
© The Author(s). 2020
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