Comparison of the central human and mouse platelet signaling cascade by systems biological analysis

Please always quote using this URN: urn:nbn:de:bvb:20-opus-230377
  • 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 comparingBackground 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.show moreshow less

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Metadaten
Author: Johannes Balkenhol, Kristin V. Kaltdorf, Elmina Mammadova-Bach, Attila Braun, Bernhard Nieswandt, Marcus Dittrich, Thomas DandekarORCiD
URN:urn:nbn:de:bvb:20-opus-230377
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Fakultät für Biologie / Rudolf-Virchow-Zentrum
Medizinische Fakultät / Institut für Experimentelle Biomedizin
Language:English
Parent Title (English):BMC Genomics
Year of Completion:2020
Volume:21
Article Number:897
Source:BMC Genomics (2020) 21:897 https://doi.org/10.1186/s12864-020-07215-4
DOI:https://doi.org/10.1186/s12864-020-07215-4
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Tag:cascade; human; interactome; interspecies comparison; mouse; network; platelet; proteome; signaling; transcriptome
Release Date:2021/04/22
Open-Access-Publikationsfonds / Förderzeitraum 2020
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International