PF4V1 Human
Description
Antiangiogenic Activity
PF4V1 inhibits endothelial cell chemotaxis and angiogenesis by disrupting VEGF signaling pathways. Its antiangiogenic potency exceeds that of PF4, making it a potential therapeutic target for cancer and retinopathies .
Immune Modulation
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Bacterial Defense: PF4V1 binds to bacterial surfaces (e.g., Staphylococcus aureus), triggering antibodies that cross-react with PF4/heparin complexes. This mechanism enhances phagocytosis and may explain heparin-induced thrombocytopenia (HIT) as a misdirected antibacterial response .
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Viral Replication: PF4V1 promotes dengue virus (DV) and Japanese encephalitis virus (JEV) replication in monocytes by suppressing IFN-α production via the p38MAPK-STAT2-IRF9 axis. Blocking PF4V1’s receptor (CXCR3) with AMG487 inhibits viral replication and improves survival in murine models .
Cognitive Enhancement
In murine studies, PF4V1 treatment enhances spatial memory and reduces age-related cognitive deficits. RNA sequencing revealed PF4V1-mediated upregulation of synaptic plasticity genes (e.g., Bdnf, Arc) in aging hippocampi .
Research Findings
Table 1: Key Studies on PF4V1
Clinical and Therapeutic Implications
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Heparin-Induced Thrombocytopenia (HIT): PF4V1-bacteria complexes may preimmunize patients, leading to rapid IgG antibody production upon heparin exposure .
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Antiviral Strategies: CXCR3 inhibitors (e.g., AMG487) block PF4V1-mediated viral replication, suggesting utility in treating flaviviral infections .
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Neurodegenerative Diseases: PF4V1 administration reverses age-related hippocampal gene expression changes, positioning it as a candidate for cognitive decline therapies .
6. Pathway Associations
PF4V1 is implicated in multiple signaling pathways:
Expression and Regulation
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Tissue Distribution: High expression in platelets, megakaryocytes, and atherosclerotic plaques .
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Inducers: Thrombin, collagen, and pathogen-associated molecular patterns (PAMPs) .
8. Challenges and Future Directions
While PF4V1’s dual role in host defense and pathology is established, challenges include:
Product Specs
Product Science Overview
Platelet Factor 4 Variant 1 (PF4-V1), also known as CXCL4L1, is a natural non-allelic gene variant of the CXC chemokine Platelet Factor 4 (PF4 or CXCL4). PF4-V1 is a recombinant protein that has been studied for its unique properties and potential therapeutic applications, particularly in the field of oncology and angiogenesis inhibition .
PF4-V1 is typically produced using recombinant DNA technology. The gene encoding PF4-V1 is cloned into an expression vector, which is then introduced into a host cell, such as E. coli. The host cells are cultured, and the recombinant protein is expressed and subsequently purified. The mature protein of PF4-V1 differs from authentic PF4 only in three carboxy-terminal amino acids, which results in distinct biological properties .
PF4-V1 exhibits different properties and cellular functions compared to PF4. It has been shown to be a potent inhibitor of angiogenesis, the process by which new blood vessels form from pre-existing vessels. This property makes PF4-V1 a promising candidate for anti-tumor therapies, as it can inhibit the growth and metastasis of various tumors by preventing the formation of new blood vessels that supply nutrients to the tumor .
PF4-V1 exerts its anti-angiogenic effects by inhibiting endothelial cell chemotaxis and proliferation. It binds to heparin-like molecules with high affinity, neutralizing their effects and promoting blood coagulation. Additionally, PF4-V1 has been shown to interact with specific receptors on the surface of endothelial cells, leading to the inhibition of angiogenesis .
The expression and activity of PF4-V1 are regulated by various factors, including cytokines and growth factors. Changes in the expression of PF4-V1 have been associated with different pathological conditions, such as cancer and inflammatory diseases. Understanding the regulatory mechanisms of PF4-V1 is crucial for developing targeted therapies that can modulate its activity for therapeutic purposes .
