Scholarship 23/08178-5 - Imunotrombose, Podoplanina - BV FAPESP
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The role of podoplanin and CLEC-2 pathway in the sickle cell disease

Grant number: 23/08178-5
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: November 01, 2023
End date until: February 28, 2026
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Erich Vinicius de Paula
Grantee:Ivanio Teixeira de Borba Junior
Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:19/18886-1 - Pathophysiological mechanisms and treatment of red blood cell abnormalities, AP.TEM
Associated scholarship(s):24/17043-9 - Exploring novel mechanisms of hemostasis activation in sickle cell disease: focus on the PDPN:CLEC-2 pathway, BE.EP.DR

Abstract

Hypercoagulability is a hallmark of sickle cell disease (SCD), and its pathophysiology is related to the concomitant activation of hemostasis and innate immunity, in a process known as immunothrombosis. Among the mechanisms involved in immunothrombosis, the best known are the generation of neutrophil extracellular networks (NETs) and the expression of tissue factor by monocytes, but over the last few years, new pathways of activation of hemostasis in the inflammatory context have been described. Podoplanin (PDPN) is a membrane protein located mainly in lymphatic vessels, and can be found in other cell types, such as fibroblasts and monocytes, whose only known PDPN ligand is CLEC-2 (C-type lectin-like type 2). This is a receptor present mainly on platelets, involved in platelet activation during inflammation. Its role in the pathophysiology of thrombosis mediated by inflammatory stimuli has been described over the last few years. Data obtained in our laboratory showed the modulation of this pathway in COVID-19. So far, this route has not been explored in the DF, which is the objective of this project. Preliminary data from our group show elevated levels of PDPN in patients with SS homozygous sickle cell anemia when compared with patients with SC hemoglobinopathy. For this purpose, we propose a detailed analysis of the podoplanin/CLEC-2 pathway through their expression in hematopoietic cells, extracellular vesicles (EVs), and in their soluble form in plasma. In addition, such results will be correlated with inflammatory and hemostatic biomarkers, as well as with clinical data on SCD. Thus, such findings would contribute to a better understanding of the pathophysiology of SCD in the context of immunothrombosis.

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