Objectives: After development and differentiation, megakaryocytes (MKs) can produce platelets. As is well known, thrombopoietin (TPO) can induce MKs to differentiate. The effect of thrombin on MKs differentiation is not clear. In this study, we used a human megakaryoblastic leukemia cell line (Meg-01) to assess the effect of thrombin on MKs differentiation.
Methods: In order to interrogate the role of thrombin in Meg-01 cells differentiation, the changes of morphology, cellular function, and expression of diverse factors were analyzed.
Results: The results show that thrombin suppresses Meg-01 cells proliferation and induces apoptosis and cell cycle arrest. Thrombin upregulates the expression of CD41b, which is one of the most important MK markers. Globin transcription factor 1 (GATA-1), an important transcriptional regulator, controls MK development and maturation. The expression of GATA-1 is also upregulated by thrombin in Meg-01 cells. The expression of B-cell lymphoma 2 (Bcl-2), an apoptosis-inhibitory protein, is downregulated by thrombin. Phosphorylated protein kinase B (p-AKT) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated by thrombin in Meg-01 cells. All the results are consistent with Meg-01 cells treated with TPO.
Discussion And Conclusion: In conclusion, all these data indicate that thrombin maybe plays an important role in MK differentiation into platelets. However, whether the platelet-like particles are certainly platelets remains unknown.
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http://dx.doi.org/10.1155/2016/9313269 | DOI Listing |
Platelets
December 2025
Department of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
Platelet-like particles (PLPs), derived from megakaryocytic cell lines MEG-01 and K-562, are widely used as a surrogate to study platelet formation and function. We demonstrate by RNA-Seq that PLPs are transcriptionally distinct from platelets. Expression of key genes in signaling pathways promoting platelet activation/aggregation, such as the PI3K/AKT, protein kinase A, phospholipase C, and α-adrenergic and GP6 receptor pathways, was missing or under-expressed in PLPs.
View Article and Find Full Text PDFBiomolecules
October 2024
College of Pharmacy, Kyungsung University, 309 Suyeong-ro, Busan 48434, Republic of Korea.
Platelets are essential blood components that maintain hemostasis, prevent excessive bleeding, and facilitate wound healing. Reduced platelet counts are implicated in various diseases, including leukemia, hepatitis, cancer, and Alzheimer's disease. Enhancing megakaryocytic differentiation is a promising strategy to increase platelet production.
View Article and Find Full Text PDFThromb Res
December 2024
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada; Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada; Cardiovascular Research Institute, University of Alberta, Edmonton, AB, Canada; Cancer Research Institute of Northern Alberta, University of Alberta, Edmonton, AB, Canada. Electronic address:
Background: Platelet-rich microvascular thrombi are common in severe COVID-19. Endogenous nitric oxide (NO)-signaling limits thrombus formation and previously we identified platelet subpopulations with a differential ability to produce NO based on the presence or absence of endothelial nitric oxide synthase (eNOS). eNOS expression is counter-regulated by cytokines, and COVID-19-associated immune/inflammatory responses may affect the transcriptome profile of megakaryocytes and their platelet progeny.
View Article and Find Full Text PDFJ Mol Cell Biol
October 2024
Centre d'Infection et d'Immunité de Lille, INSERM U1019, CNRS UMR9017, Institut Pasteur de Lille, Lille 59019, France.
Despite an undetectable plasma viral load as a result of antiretroviral therapy, HIV-1-infected individuals with poor immune reconstitution harbor infectious HIV-1 within their platelets. Megakaryocytes, as platelet precursors, are the likely cellular origin of these HIV-1-containing platelets. To investigate the mechanisms that allow megakaryocytes to support HIV-1 infection, we established in vitro models of viral infection using hematopoietic stem cell-derived megakaryocytes and the megakaryocytic MEG-01 cell line.
View Article and Find Full Text PDFHeliyon
August 2024
Department of Transfusion Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Background: Type 2 diabetes mellitus (T2DM) presents a thrombotic environment, contributing to diabetic macroangiopathy and microangiopathy. In this study, the regulation of microthrombosis in T2DM was assessed.
Methods: Platelets from T2DM patients and healthy controls were analyzed using 4D label-free proteomics and bioinformatics.
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