Key result
Systems biological analysis revealed that while the central platelet signaling cascade is genetically conserved, there are major species-specific differences in mRNA and protein expression levels between humans and mice.
Why the study?
Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research.
Significant species-specific differences exist in the central platelet signaling cascade between humans and mice, which may limit the transferability of murine thrombosis models to human physiology.
Species differences limit murine thrombosis model transferability to humans; challenges assumptions of signaling conservation in translational studies.
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 uniprot 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.
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Balkenhol et al. (2020) studied Platelet signaling cascade. Human platelet signaling cascade vs. Mouse platelet signaling cascade was evaluated on mRNA and protein expression differences. Systems biological analysis revealed that while the central platelet signaling cascade is genetically conserved, there are major species-specific differences in mRNA and protein expression levels between humans and mice.
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