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Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
Published on: November 22, 2024
Glycogen synthase kinase-3 negatively regulates tissue factor expression in monocytes interacting with activated
A Di Santo1, C Amore, G Dell'Elba
1Laboratory of Vascular Biology and Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
Journal of Thrombosis and Haemostasis : JTH
|February 16, 2011
Summary
Glycogen synthase kinase 3 (GSK3) normally inhibits tissue factor (TF) expression in monocytes interacting with platelets. Insulin signaling, via PI(3)K, overcomes this inhibition, promoting TF and thrombus formation.
Area of Science:
- Cellular signaling pathways
- Thrombosis and hemostasis
- Molecular mechanisms of coagulation
Background:
- Monocytes (MN) and platelets (PLT) interact at vascular injury sites to synthesize tissue factor (TF), promoting thrombus formation.
- Intracellular signaling pathways regulating TF expression in MN during thrombosis are not fully understood.
Purpose of the Study:
- To investigate the role of glycogen synthase kinase 3 (GSK3) and the downstream insulin receptor pathway in platelet-induced TF expression in monocytes.
- To elucidate the molecular mechanisms linking metabolic disorders to thrombotic risk.
Main Methods:
- Utilized an in vitro model of human MN-PLT interactions.
- Analyzed TF activity, protein, and gene expression kinetics.
- Employed pharmacological inhibitors of GSK3 and phosphoinositide-3 kinase (PI(3)K).
Main Results:
- TF expression in MN-PLT interactions increased significantly after 8-10 hours.
- GSK3β phosphorylation (inactivating) correlated with TF expression kinetics.
- GSK3 inhibition and PI(3)K blockade altered TF expression and NF-kB nuclear accumulation.
- Insulin enhanced PLT-induced TF expression in a PI(3)K-dependent manner.
Conclusions:
- GSK3 acts as a "molecular brake" on TF expression in MN interacting with activated PLT.
- PI(3)K signaling, through Akt-dependent GSK3 phosphorylation, relieves this brake, enabling TF gene expression.
- Identified a novel link between thrombotic risk and metabolic disorders via the insulin-GSK3-PI(3)K pathway.
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