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Molecular Research in Platelet Biology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 September 2024 | Viewed by 1094

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Guest Editor
Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA
Interests: platelets; sepsis; infection; thrombosis; hemostasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Platelets are anucleate cells that are derived mainly from bone marrow megakaryocytes. While the most described role for platelets is in arterial thrombosis and hemostasis, recent literature has revealed new functions of this small but important cell. In fact, platelets regulate a diverse set of processes including immunity, inflammation, vascular integrity, and atherosclerosis, among others. Therefore, we are preparing a new issue in IJMS called Molecular Research in Platelet Biology! This is a broad topic and will allow for submissions covering many different topics related to platelet biology. Reviews or original research are welcome and can include topics from platelet aggregation to immune-mediated platelet activation, and everything in between. The role of specific platelet receptors and the downstream signalling governing platelet function are also a welcome topic.

Dr. John Kostyak
Guest Editor

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Keywords

  • platelets
  • aggregation
  • adhesion
  • thrombosis
  • hemostasis

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Published Papers (1 paper)

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Research

17 pages, 2443 KiB  
Article
Pim Kinase Inhibition Disrupts CXCR4 Signalling in Megakaryocytes and Platelets by Reducing Receptor Availability at the Surface
by Sophie H. Nock, Maria R. Blanco-Lopez, Chloe Stephenson-Deakin, Sarah Jones and Amanda J. Unsworth
Int. J. Mol. Sci. 2024, 25(14), 7606; https://doi.org/10.3390/ijms25147606 - 11 Jul 2024
Viewed by 822
Abstract
A key step in platelet production is the migration of megakaryocytes to the vascular sinusoids within the bone marrow. This homing is mediated by the chemokine CXCL12 and its receptor CXCR4. CXCR4 is also a positive regulator of platelet activation and thrombosis. Pim-1 [...] Read more.
A key step in platelet production is the migration of megakaryocytes to the vascular sinusoids within the bone marrow. This homing is mediated by the chemokine CXCL12 and its receptor CXCR4. CXCR4 is also a positive regulator of platelet activation and thrombosis. Pim-1 kinase has been shown to regulate CXCR4 signalling in other cell types, and we have previously described how Pim kinase inhibitors attenuate platelet aggregation to CXCL12. However, the mechanism by which Pim-1 regulates CXCR4 signalling in platelets and megakaryocytes has yet to be elucidated. Using human platelets, murine bone marrow-derived megakaryocytes, and the megakaryocyte cell line MEG-01, we demonstrate that pharmacological Pim kinase inhibition leads to reduced megakaryocyte and platelet function responses to CXCL12, including reduced megakaryocyte migration and platelet granule secretion. Attenuation of CXCL12 signalling was found to be attributed to the reduced surface expression of CXCR4. The decrease in CXCR4 surface levels was found to be mediated by rapid receptor internalisation, in the absence of agonist stimulation. We demonstrate that pharmacological Pim kinase inhibition disrupts megakaryocyte and platelet function by reducing constitutive CXCR4 surface expression, decreasing the number of receptors available for agonist stimulation and signalling. These findings have implications for the development and use of Pim kinase inhibitors for the treatment of conditions associated with elevated circulating levels of CXCL12/SDF1α and increased thrombotic risk. Full article
(This article belongs to the Special Issue Molecular Research in Platelet Biology)
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