ArticleInternational journal of molecular sciences2022
PAR4-Mediated PI3K/Akt and RhoA/ROCK Signaling Pathways Are Essential for Thrombin-Induced Morphological Changes in MEG-01 Cells.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 10 citations in OpenAlex.
- Gestodene Accelerates Cutaneous Wound Healing via PAR1-Selective Positive Allosteric Modulation.International journal of molecular sciences · 2026Article
- Mitochondrial CaCommunications biology · 2026Article
- An activity labelled molecular networking strategy-assisted discovery of antiplatelet aggregation-active components fromFrontiers in nutrition · 2026Article
- GPD2 inhibition impairs coagulation function via ROS/NF-κB/P2Y12 pathway.Cellular & molecular biology letters · 2025Article
- Endothelial protease-activated receptor 4: impotent or important?Frontiers in cardiovascular medicine · 2025Review
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Unraveling the Molecular Mechanisms of Activated Protein C (APC) in Mitigating Reperfusion Injury and Cardiac Ischemia: a Promising Avenue for Novel Therapeutic Interventions.Journal of cardiovascular translational research · 2024Review
- MicroRNA-26a alleviates tubulointerstitial fibrosis in diabetic kidney disease by targeting PAR4.Journal of cellular and molecular medicine · 2024Article
- Gestodene, a novel positive allosteric modulator of PAR1, enhances PAR1-mediated human platelet aggregation.Frontiers in pharmacology · 2024Article
- Thrombopoietin-independent generation of platelet-like particles from megakaryoblastic cells.Scientific reports · 2023Article
- Elucidation of Phytochemicals Affecting Platelet Responsiveness in Dangguisu-san: Active Ingredient Prediction and Experimental Research Using Network Pharmacology.Plants (Basel, Switzerland) · 2023Article
- Berbamine Reduces Chloroquine-Induced Itch in Mice through Inhibition of MrgprX1.International journal of molecular sciences · 2022Article
- Downregulating ROCK2 by human umbilical cord mesenchymal stem cells promotes pro-resolving microglial polarization and alleviates cerebral injury in germinal matrix hemorrhage.Cell transplantationArticle
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Thrombin stimulates platelets via a dual receptor system of protease-activated receptors (PARs): PAR1 and PAR4. PAR1 activation induces a rapid and transient signal associated with the initiation of platelet aggregation, whereas PAR4 activation results in a prolonged signal, required for later phases, that regulates the stable formation of thrombus. In this study, we observed differential signaling pathways for thrombin-induced PAR1 and PAR4 activation in a human megakaryoblastic leukemia cell line, MEG-01. Interestingly, thrombin induced both calcium signaling and morphological changes in MEG-01 cells via the activation of PAR1 and PAR4, and these intracellular events were very similar to those observed in platelets shown in previous studies. We developed a novel image-based assay to quantitatively measure the morphological changes in living cells, and observed the underlying mechanism for PAR1- and PAR4-mediated morphological changes in MEG-01 cells. Selective inhibition of PAR1 and PAR4 by vorapaxar and BMS-986120, respectively, showed that thrombin-induced morphological changes were primarily mediated by PAR4 activation. Treatment of a set of kinase inhibitors and 2-aminoethoxydiphenyl borate (2-APB) revealed that thrombin-mediated morphological changes were primarily regulated by calcium-independent pathways and PAR4 activation-induced PI3K/Akt and RhoA/ROCK signaling pathways in MEG-01 cells. These results indicate the importance of PAR4-mediated signaling pathways in thrombin-induced morphological changes in MEG-01 cells and provide a useful in vitro cellular model for platelet research.
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