NEW MECHANISMS FOR REGULATING PLATELET REACTIVITY IN NEONATES (Q3171007): Difference between revisions
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(Removed claim: summary (P836): Platelets play a fundamental role in haemostasis and alterations in their reactivity have been associated with the development of thrombotic and hemorrhagic processes. The platelets of neonates (PN), vs adult (PA) platelets, are hyporeactive compared to most physiological agonists, constituting an ideal model for investigating the mechanisms that control platelet reactivity, which are still poorly characterised. Our objective is to identify me...) |
(Created claim: summary (P836): Platelets play a fundamental role in haemostasis and alterations in their reactivity have been associated with the development of thrombotic and hemorrhagic processes. The platelets of neonates (PN), vs adult (PA) platelets, are hyporeactive compared to most physiological agonists, constituting an ideal model for investigating the mechanisms that control platelet reactivity, which are still poorly characterised. Our objective is to identify mech...) |
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Platelets play a fundamental role in haemostasis and alterations in their reactivity have been associated with the development of thrombotic and hemorrhagic processes. The platelets of neonates (PN), vs adult (PA) platelets, are hyporeactive compared to most physiological agonists, constituting an ideal model for investigating the mechanisms that control platelet reactivity, which are still poorly characterised. Our objective is to identify mechanisms that control the differences in reactivity between PN and BP with novel approaches: starting from a gene expression array and a miRNA array in PN vs PA, we have identified miRNA whose levels are negatively correlated with target mRNA corresponding to proteins involved in platelet reactivity and differently expressed between PN and PA (miR-30c:ADRA2A; miR433: STX11; Mir-539: STX11 and miR-940; RANBP10). Validated the differences in expression of the pairs selected by qRT-PCR, we now intend to validate them functionally in cell models; investigate differences between PN and PA in the levels of expression or functionality of G proteins, mediators for the signalling of most agonists (ADP, TxA2, thrombin) and their regulatory proteins (RGS), as well as receptors with ITAM domains (GPVI, FcgRII, Clec-2) and ITIM (PECAM-1); C) We will evaluate platelet inhibition pathways (PGE1/cAMP/PKA, SNP/cGMP/PKG) in PN, as its deregulation can also modulate platelet reactivity. Our results will help to understand the role of these elements in the reactivity of NPs, completely unknown, and could serve to identify new therapeutic targets. (English) | |||||||||||||||
| Property / summary: Platelets play a fundamental role in haemostasis and alterations in their reactivity have been associated with the development of thrombotic and hemorrhagic processes. The platelets of neonates (PN), vs adult (PA) platelets, are hyporeactive compared to most physiological agonists, constituting an ideal model for investigating the mechanisms that control platelet reactivity, which are still poorly characterised. Our objective is to identify mechanisms that control the differences in reactivity between PN and BP with novel approaches: starting from a gene expression array and a miRNA array in PN vs PA, we have identified miRNA whose levels are negatively correlated with target mRNA corresponding to proteins involved in platelet reactivity and differently expressed between PN and PA (miR-30c:ADRA2A; miR433: STX11; Mir-539: STX11 and miR-940; RANBP10). Validated the differences in expression of the pairs selected by qRT-PCR, we now intend to validate them functionally in cell models; investigate differences between PN and PA in the levels of expression or functionality of G proteins, mediators for the signalling of most agonists (ADP, TxA2, thrombin) and their regulatory proteins (RGS), as well as receptors with ITAM domains (GPVI, FcgRII, Clec-2) and ITIM (PECAM-1); C) We will evaluate platelet inhibition pathways (PGE1/cAMP/PKA, SNP/cGMP/PKG) in PN, as its deregulation can also modulate platelet reactivity. Our results will help to understand the role of these elements in the reactivity of NPs, completely unknown, and could serve to identify new therapeutic targets. (English) / rank | |||||||||||||||
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| Property / summary: Platelets play a fundamental role in haemostasis and alterations in their reactivity have been associated with the development of thrombotic and hemorrhagic processes. The platelets of neonates (PN), vs adult (PA) platelets, are hyporeactive compared to most physiological agonists, constituting an ideal model for investigating the mechanisms that control platelet reactivity, which are still poorly characterised. Our objective is to identify mechanisms that control the differences in reactivity between PN and BP with novel approaches: starting from a gene expression array and a miRNA array in PN vs PA, we have identified miRNA whose levels are negatively correlated with target mRNA corresponding to proteins involved in platelet reactivity and differently expressed between PN and PA (miR-30c:ADRA2A; miR433: STX11; Mir-539: STX11 and miR-940; RANBP10). Validated the differences in expression of the pairs selected by qRT-PCR, we now intend to validate them functionally in cell models; investigate differences between PN and PA in the levels of expression or functionality of G proteins, mediators for the signalling of most agonists (ADP, TxA2, thrombin) and their regulatory proteins (RGS), as well as receptors with ITAM domains (GPVI, FcgRII, Clec-2) and ITIM (PECAM-1); C) We will evaluate platelet inhibition pathways (PGE1/cAMP/PKA, SNP/cGMP/PKG) in PN, as its deregulation can also modulate platelet reactivity. Our results will help to understand the role of these elements in the reactivity of NPs, completely unknown, and could serve to identify new therapeutic targets. (English) / qualifier | |||||||||||||||
point in time: 12 October 2021
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Revision as of 18:57, 12 October 2021
Project Q3171007 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | NEW MECHANISMS FOR REGULATING PLATELET REACTIVITY IN NEONATES |
Project Q3171007 in Spain |
Statements
54,000.0 Euro
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67,500.0 Euro
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80.0 percent
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1 January 2015
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31 December 2018
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FUNDACION PARA LA FORMACION E INVESTIGACION SANITARIAS DE LA REGION DE MURCIA (FFIS)
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37°59'32.57"N, 1°7'49.94"W
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30030
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Las plaquetas tienen un papel fundamental en la hemostasia y las alteraciones en su reactividad se han asociado con el desarrollo de procesos trombóticos y hemorrágicos. Las plaquetas de los neonatos (PN), vs las de adulto (PA), son hiporreactivas frente a la mayoría de los agonistas fisiológicos, constituyendo un modelo ideal donde investigar los mecanismos que controlan la reactividad plaquetaria, aún poco caracterizados. Nuestro objetivo es identificar mecanismos que controlan las diferencias de reactividad entre PN y PA con aproximaciones novedosas: a) Partiendo de un array de expresión génica y de un array de miRNA en PN vs PA, hemos identificado miRNA cuyos niveles se correlacionen negativamente con mRNA diana correspondientes a proteínas implicadas en reactividad plaquetaria y diferentemente expresados entre PN y PA (miR-30c:ADRA2A; miR433: STX11; miR-539: STX11 y miR-940; RANBP10). Validadas las diferencias de expresión de los pares seleccionados por qRT-PCR, pretendemos ahora la validación funcional de los mismos en modelos celulares; b) Investigaremos diferencias entre PN y PA en los niveles de expresión y/o funcionalidad de proteínas G, mediadoras de la señalización de la mayoría de agonistas (ADP, TxA2, trombina) y de sus proteínas reguladoras (RGS), así como de receptores con dominios ITAM (GPVI, FcgRII, Clec-2) e ITIM (PECAM-1); c) Evaluaremos vías de inhibición plaquetaria (PGE1/cAMP/PKA, SNP/cGMP/PKG) en PN, pues su desregulación puede modular también la reactividad plaquetaria. Nuestros resultados ayudarán a conocer el papel de estos elementos en la reactividad de las PN, completamente desconocido, y podrían servir para identificar nuevas dianas terapéuticas. (Spanish)
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Platelets play a fundamental role in haemostasis and alterations in their reactivity have been associated with the development of thrombotic and hemorrhagic processes. The platelets of neonates (PN), vs adult (PA) platelets, are hyporeactive compared to most physiological agonists, constituting an ideal model for investigating the mechanisms that control platelet reactivity, which are still poorly characterised. Our objective is to identify mechanisms that control the differences in reactivity between PN and BP with novel approaches: starting from a gene expression array and a miRNA array in PN vs PA, we have identified miRNA whose levels are negatively correlated with target mRNA corresponding to proteins involved in platelet reactivity and differently expressed between PN and PA (miR-30c:ADRA2A; miR433: STX11; Mir-539: STX11 and miR-940; RANBP10). Validated the differences in expression of the pairs selected by qRT-PCR, we now intend to validate them functionally in cell models; investigate differences between PN and PA in the levels of expression or functionality of G proteins, mediators for the signalling of most agonists (ADP, TxA2, thrombin) and their regulatory proteins (RGS), as well as receptors with ITAM domains (GPVI, FcgRII, Clec-2) and ITIM (PECAM-1); C) We will evaluate platelet inhibition pathways (PGE1/cAMP/PKA, SNP/cGMP/PKG) in PN, as its deregulation can also modulate platelet reactivity. Our results will help to understand the role of these elements in the reactivity of NPs, completely unknown, and could serve to identify new therapeutic targets. (English)
12 October 2021
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Murcia
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Identifiers
PI14_01956
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