Cargando…
Comparison of the central human and mouse platelet signaling cascade by systems biological analysis
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 systemsbio...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756956/ https://www.ncbi.nlm.nih.gov/pubmed/33353544 http://dx.doi.org/10.1186/s12864-020-07215-4 |
_version_ | 1783626652300869632 |
---|---|
author | Balkenhol, Johannes Kaltdorf, Kristin V. Mammadova-Bach, Elmina Braun, Attila Nieswandt, Bernhard Dittrich, Marcus Dandekar, Thomas |
author_facet | Balkenhol, Johannes Kaltdorf, Kristin V. Mammadova-Bach, Elmina Braun, Attila Nieswandt, Bernhard Dittrich, Marcus Dandekar, Thomas |
author_sort | Balkenhol, Johannes |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-020-07215-4. |
format | Online Article Text |
id | pubmed-7756956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-77569562020-12-28 Comparison of the central human and mouse platelet signaling cascade by systems biological analysis Balkenhol, Johannes Kaltdorf, Kristin V. Mammadova-Bach, Elmina Braun, Attila Nieswandt, Bernhard Dittrich, Marcus Dandekar, Thomas BMC Genomics Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-020-07215-4. BioMed Central 2020-12-22 /pmc/articles/PMC7756956/ /pubmed/33353544 http://dx.doi.org/10.1186/s12864-020-07215-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Balkenhol, Johannes Kaltdorf, Kristin V. Mammadova-Bach, Elmina Braun, Attila Nieswandt, Bernhard Dittrich, Marcus Dandekar, Thomas Comparison of the central human and mouse platelet signaling cascade by systems biological analysis |
title | Comparison of the central human and mouse platelet signaling cascade by systems biological analysis |
title_full | Comparison of the central human and mouse platelet signaling cascade by systems biological analysis |
title_fullStr | Comparison of the central human and mouse platelet signaling cascade by systems biological analysis |
title_full_unstemmed | Comparison of the central human and mouse platelet signaling cascade by systems biological analysis |
title_short | Comparison of the central human and mouse platelet signaling cascade by systems biological analysis |
title_sort | comparison of the central human and mouse platelet signaling cascade by systems biological analysis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756956/ https://www.ncbi.nlm.nih.gov/pubmed/33353544 http://dx.doi.org/10.1186/s12864-020-07215-4 |
work_keys_str_mv | AT balkenholjohannes comparisonofthecentralhumanandmouseplateletsignalingcascadebysystemsbiologicalanalysis AT kaltdorfkristinv comparisonofthecentralhumanandmouseplateletsignalingcascadebysystemsbiologicalanalysis AT mammadovabachelmina comparisonofthecentralhumanandmouseplateletsignalingcascadebysystemsbiologicalanalysis AT braunattila comparisonofthecentralhumanandmouseplateletsignalingcascadebysystemsbiologicalanalysis AT nieswandtbernhard comparisonofthecentralhumanandmouseplateletsignalingcascadebysystemsbiologicalanalysis AT dittrichmarcus comparisonofthecentralhumanandmouseplateletsignalingcascadebysystemsbiologicalanalysis AT dandekarthomas comparisonofthecentralhumanandmouseplateletsignalingcascadebysystemsbiologicalanalysis |