Functional Genomics and Systems Biology Group, Department of Bioinformatics, Biocenter, Am Hubland, University of Würzburg, D-97074, Würzburg, Germany.
Institute of Experimental Biomedicine, University Hospital and Rudolf Virchow Centre, University of Würzburg, Würzburg, Germany.
BMC Genomics. 2020 Dec 22;21(1):897. doi: 10.1186/s12864-020-07215-4.
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).
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.
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.
理解血小板激活和聚集的分子机制对于基础和临床止血和血栓形成研究具有重要意义。中央血小板蛋白相互作用网络参与了对外源性因素的主要反应。通过系统生物学途径分析，这被定义为血小板的中央调节信号级联（CC）。
本文系统比较了小鼠和人类之间的 CC，发现了主要差异。通过比较同源的人类和小鼠基因来分析遗传差异。接下来，我们分析了不同的 mRNA 表达水平。考虑到 4 个小鼠和 7 个人类高质量蛋白质组数据集，我们确定了那些主要的 mRNA 表达差异（81%），这些差异得到了蛋白质组数据的支持。CC 在遗传完整性方面是保守的，但我们观察到两种物种之间在 mRNA 和蛋白质水平上存在很大差异。观察中央相互作用物，人类 PLCB2、MMP9、BDNF、ITPR3 和 SLC25A6（始终使用 Entrez 符号）在所有鼠数据集均不存在。CC 相互作用物 GNG12、PRKCE 和 ADCY9 仅在小鼠中出现。观察共同蛋白质，TLN1、CALM3、PRKCB、APP、SOD2 和 TIMP1 在人类中丰度更高，而 RASGRP2、ITGB2、MYL9、EIF4EBP1、ADAM17、ARRB2、CD9 和 ZYX 在小鼠中丰度更高。关键激酶 SRC 在 mRNA 和蛋白质水平上的调节以及 ADP 受体 P2RY12 也存在不同。
我们的结果强调了血小板信号在物种特异性上的差异，以及人类血小板中特定精细调节的靶点和小鼠特异性信号差异。
