FLT1 D3 Human
Description
Biological Function and Mechanism
FLT1 D3 Human mimics the soluble isoform of VEGFR-1 (sVEGFR-1), which acts as a decoy receptor for VEGF-A. Key functional insights:
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VEGF Binding: Binds VEGF-A with high affinity (comparable to full-length Flt1) but lacks signaling capability due to the absence of intracellular domains .
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Angiogenic Regulation:
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Inhibits VEGF-VEGFR-2 (KDR) Interaction: Reduces pro-angiogenic signaling by sequestering VEGF-A, thereby suppressing endothelial cell proliferation and migration .
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Isoform-Specific Effects: Shifts toward FLT1 D3 expression (e.g., via alternative splicing) enhances angiogenesis in ischemic tissues by releasing VEGF-A from inhibition .
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Role in Ischemic Tissue Repair
A 2024 study demonstrated that mice with constitutive FLT1 D3 expression showed:
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Accelerated Angiogenesis: Increased CD31+ capillary density in ischemic limbs and hearts .
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Reduced Inflammation: Lower macrophage infiltration in injured muscles .
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Mechanism: Enhanced VEGF-A availability for VEGFR-2 signaling in endothelial cells .
Muscle Stem Cell Survival
FLT1 D3 Human modulates the VEGF-A-FLT1-AKT1 pathway in muscle stem cells (MuSCs), promoting survival during regeneration :
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Apoptosis Resistance: Recombinant VEGF-A + FLT1-FC fusion protein rescues MuSCs from thapsigargin-induced apoptosis .
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Dystrophy Models: Flt1 deletion in mdx mice (Duchenne muscular dystrophy) improves muscle function, linked to enhanced capillary density and MuSC survival .
Retinal Neovascularization
In human retinal microvascular endothelial cells:
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VEGF-A Signaling: Primarily activates KDR (VEGFR-2) for proliferation and migration, while FLT1 D3 suppresses these processes .
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Synergy with Other Receptors: Both KDR and FLT1 are required for phospholipase D (PLD) activation downstream of VEGF-A .
Clinical and Research Implications
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Therapeutic Target: Modulating FLT1 D3 expression could enhance angiogenesis in ischemic diseases (e.g., heart attack, peripheral artery disease) .
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Drug Development: Recombinant FLT1 D3 may serve as a tool to study VEGF signaling or as a decoy in anti-angiogenic therapies .
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Experimental Models: Used in tube formation assays, apoptosis studies, and gene knockout mice to dissect VEGF receptor crosstalk .
Product Specs
SKLKDPELSLKGTQHIMQAGQTLHLQCRGEAAHKWSLPEMVSKESERLSI TKSACGRNGKQFCSTLTLNTAQANHTGFYSCKYLAVPTSKKKETESAIYI FISDTGRPFVEMYSEIPEIIHMTEGRELVIPCRVTSPNITVTLKKFPLDT LIPDGKRIIWDSRKGFIISNATYKEIGLLTCEATVNGHLYKTNYLTHRQT NTIIDVQISTPRPVKLLRGHTLVLNCTATTPLNTRVQMTWSYPDEKNKRA SVRRRIDQSNSHANIFYSVLTIDKMQNKDKGLYTCRVRSGPSFKSVNTSV HIYDKAFITVKHRKQQVLETVAGKRSY.
Q&A
Experimental Design for FLT1 D3 Human Studies
Q: How should I design experiments to study the role of FLT1 D3 Human in vascular endothelial growth factor (VEGF) signaling? A: To study FLT1 D3 Human, design experiments that involve the use of recombinant FLT1 D3 proteins to assess their binding affinity to VEGF. This can be achieved through techniques like ELISA or surface plasmon resonance (SPR). Additionally, cell-based assays using endothelial cells can help evaluate the biological activity of FLT1 D3 in inhibiting VEGF-induced cell proliferation .
Data Analysis and Contradiction Resolution
Q: How do I resolve contradictions in data regarding FLT1 D3 Human's role in different cell types? A: Resolve data contradictions by carefully examining experimental conditions, such as cell types and VEGF isoforms used. Consider factors like cell culture conditions, the presence of other growth factors, and the specific FLT1 isoforms expressed. Use statistical methods to compare results across studies and consider meta-analysis if necessary .
Advanced Research Questions: FLT1 D3 Human and Disease Models
Q: What advanced research approaches can be used to study FLT1 D3 Human in disease models, such as preeclampsia? A: Advanced research approaches include using animal models (e.g., mice) to study the role of FLT1 D3 in diseases like preeclampsia. Techniques such as RNA interference (RNAi) can be employed to modulate FLT1 expression in these models. Additionally, transcriptome-wide analyses can help identify genes regulated by FLT1 D3 in disease contexts .
Methodological Considerations for FLT1 D3 Human Purification
Q: What are the best methods for purifying FLT1 D3 Human protein for research use? A: FLT1 D3 Human protein is typically purified using proprietary chromatographic techniques. Ensure high purity (>90%) by analyzing the protein using SDS-PAGE and RP-HPLC. Storage conditions should be optimized to maintain protein stability, such as storing at -20°C to avoid freeze-thaw cycles .
Biological Activity Assays for FLT1 D3 Human
Q: How can I assess the biological activity of FLT1 D3 Human in inhibiting VEGF-induced cell proliferation? A: Assess biological activity by using assays that measure the inhibition of VEGF-165-induced proliferation of human umbilical vein endothelial cells (HUVECs). This involves incubating HUVECs with VEGF-165 in the presence or absence of FLT1 D3 and measuring cell proliferation using techniques like MTT or BrdU incorporation assays .
FLT1 D3 Human in Neuronal Studies
Q: What role does FLT1 D3 Human play in neuronal protection, and how can it be studied? A: FLT1 D3 Human may play a role in neuronal protection through its interaction with VEGF-B. Studies can involve primary dorsal root ganglion (DRG) cultures to assess neuronal stress and susceptibility to paclitaxel-induced cell death in the absence of FLT1 or VEGF-B. Behavioral tests like the pinprick test can also be used in animal models to evaluate neuropathy .
FLT1 D3 Human and Gene Regulation
Q: How does FLT1 D3 Human influence gene regulation in vascular development? A: FLT1 D3 Human influences gene regulation by modulating VEGF signaling pathways crucial for vascular development. Deletion of regulatory elements associated with FLT1 can lead to differential gene expression affecting blood vessel development and extracellular matrix organization. Use gene ontology (GO) terms to analyze affected pathways .
FLT1 D3 Human in Preeclampsia Research
Q: How is FLT1 D3 Human involved in preeclampsia, and what research approaches can be used to study this? A: FLT1 D3 Human is involved in preeclampsia through the production of soluble FLT1 proteins, which are anti-angiogenic factors. Research approaches include analyzing transcriptome-wide polyadenylation site sequencing (PAS-Seq) to identify mRNA isoforms associated with preeclampsia. RNAi techniques can be used to target specific FLT1 isoforms for therapeutic intervention .
FLT1 D3 Human Protein Stability and Storage
Q: What are the optimal storage conditions for FLT1 D3 Human protein to maintain its stability? A: Optimal storage conditions for FLT1 D3 Human protein involve storing it at -20°C to prevent degradation. For short-term use, store at 4°C. Avoid freeze-thaw cycles, and consider adding carrier proteins like HSA or BSA for long-term storage .
Advanced Techniques for FLT1 D3 Human Expression Analysis
Q: What advanced techniques can be used to analyze FLT1 D3 Human expression in different tissues? A: Advanced techniques include quantitative PCR (qPCR) and RNA sequencing to analyze FLT1 D3 expression levels. Immunohistochemistry can be used to localize FLT1 D3 expression in specific tissues. Consider using bioinformatics tools to analyze large datasets and identify patterns of expression across different conditions .
Example Data Table: FLT1 D3 Human Protein Characteristics
| Characteristics | Description |
|---|---|
| Molecular Mass | Approximately 45 kDa (Prospec Bio: 38.16 kDa) |
| Amino Acids | 327 amino acids (Prospec Bio: 298 amino acids fragment) |
| Purification | Proprietary chromatographic techniques |
| Storage | -20°C for long-term; 4°C for short-term use |
| Purity | >90% (SDS-PAGE and RP-HPLC) |
Example Research Findings: FLT1 D3 Human in Vascular Development
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Key Findings: FLT1 D3 Human plays a crucial role in vascular development by regulating VEGF signaling pathways.
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Methodology: Use recombinant FLT1 D3 proteins in cell-based assays to evaluate its role in inhibiting VEGF-induced cell proliferation.
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Implications: Understanding FLT1 D3 Human's function can provide insights into vascular diseases and potential therapeutic targets.
Product Science Overview
Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1), also known as Fms-like tyrosine kinase 1 (FLT1), is a receptor tyrosine kinase that plays a crucial role in the regulation of angiogenesis, the process by which new blood vessels form from pre-existing vessels. This receptor is part of the VEGFR family, which includes VEGFR-1, VEGFR-2, and VEGFR-3, each with distinct roles in vascular development and function .
VEGFR-1 is characterized by its seven immunoglobulin (Ig)-like domains, a single transmembrane domain, and an intracellular tyrosine kinase domain. The receptor binds to various ligands, including VEGFA, VEGFB, and placental growth factor (PlGF), mediating a range of biological processes such as endothelial cell proliferation, migration, and survival .
The discovery of VEGFR-1 dates back to the early 1990s when it was identified as a functional receptor for VEGFA. Subsequent research revealed its high affinity for VEGFA, suggesting its role as a decoy receptor that modulates VEGFA signaling by sequestering the ligand and preventing its interaction with VEGFR-2 . This regulatory mechanism is essential for maintaining the balance of angiogenic signals in various physiological and pathological conditions.
The recombinant form of VEGFR-1 D3 (Human) is a truncated version of the receptor, encompassing specific extracellular domains responsible for ligand binding. This recombinant protein is produced using advanced expression systems, such as HEK293 cells, to ensure high purity and functionality . The recombinant VEGFR-1 D3 is widely used in research to study its interactions with VEGF ligands and to develop therapeutic strategies targeting angiogenesis-related diseases.
VEGFR-1 D3 (Human Recombinant) is a valuable tool in both basic and applied research. It is used in binding studies to investigate the interactions between VEGFR-1 and its ligands, providing insights into the molecular mechanisms underlying angiogenesis . Additionally, this recombinant protein is employed in the development of anti-angiogenic therapies for conditions such as cancer and age-related macular degeneration, where pathological angiogenesis plays a critical role .
