VEGI Human
Description
Product Specs
MQLTKGRLHFSHPLSHTKHISPFVTDAPLRADGDKPRAHL
TVVRQTPTQHFKNQFPALHWEHELGLAFTKNRMNYTNKF
LLIPESGDYFIYSQVTFRGMTSECSEIRQAGRPNKPDSIT
VVITKVTDSYPEPTQLLMGTKSVCEVGSNWFQPIYLGAM
FSLQEGDKLMVNVSDISLVDYTKEDKTFFGAFLL.
Q&A
What is VEGI and how does it relate to TNFSF15?
VEGI (Vascular Endothelial Growth Inhibitor) is identified as a member of the tumor necrosis factor superfamily, specifically designated as TNFSF15. The protein was initially discovered as an endothelial cell-specific molecule with anti-angiogenic properties. In scientific literature, it may also be referenced by its alternative designation TL1 . Immunohistochemical analysis indicates that VEGI expression is largely limited to endothelial cells, suggesting its role as an endogenous regulator of vascular biology .
What are the known isoforms of human VEGI?
Human VEGI exists in multiple isoforms, with VEGI-192 being one of the most extensively studied. The numerical designation typically refers to the amino acid length of the protein. VEGI-192 has demonstrated significant anti-angiogenic and anti-cancer activities in experimental models . While the search results don't provide comprehensive information about all isoforms, the research focuses particularly on VEGI-192's biological activities and therapeutic potential.
What biological roles does VEGI/TNFSF15 play in human physiology?
VEGI/TNFSF15 exhibits at least two significant biological functions:
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Anti-angiogenic activity: VEGI functions as an endogenous inhibitor of angiogenesis. Research has demonstrated that it specifically eliminates tumor endothelial cells while preserving vascular smooth muscle cells, which remain associated with residual vascular basement membrane structures .
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Haematopoietic stem cell support: TNFSF15 facilitates human umbilical cord blood haematopoietic stem cell expansion, indicating a role in stem cell biology distinct from its anti-angiogenic function .
These dual roles suggest that VEGI/TNFSF15 has context-dependent functions potentially regulated by specific tissue microenvironments or receptor availability.
How do researchers distinguish between vegetarian dietary patterns in VEGI-related studies?
While not directly related to VEGI protein research, understanding dietary classification is important for nutritional studies that may examine correlations with biomarkers. When conducting population studies that might include VEGI measurements, researchers typically categorize vegetarians as:
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Lacto-vegetarians: Consume plant-based foods and dairy products
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Ovo-vegetarians: Include eggs but not dairy
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Lacto-ovo vegetarians: Consume both dairy and eggs
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Vegans: Eat only plant-based foods, excluding all animal products
This classification is relevant when studying relationships between dietary patterns and biomarkers or disease states that might involve VEGI pathways.
What experimental models are most effective for studying VEGI's anti-angiogenic properties?
Based on published research, several experimental models have proven effective for studying VEGI's anti-angiogenic properties:
The Lewis lung cancer murine model has been particularly informative, allowing assessment of both therapeutic efficacy and mechanistic insights into VEGI's selective effects on tumor vasculature .
How does VEGI-192 specifically eliminate tumor endothelial cells while preserving vascular smooth muscle cells?
VEGI-192 demonstrates remarkable selectivity in its anti-vascular effects. Research shows that VEGI treatment eliminates tumor endothelial cells but not vascular smooth muscle cells, which remain associated with residual vascular structures consisting of basement membrane .
This selectivity suggests several possible mechanisms:
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Differential receptor expression between endothelial and smooth muscle cells
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Cell type-specific signaling pathways activated by VEGI
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Unique vulnerability of proliferating endothelial cells compared to quiescent smooth muscle cells
The finding that VEGI expression is largely limited to endothelial cells suggests it may function as an autocrine regulator of endothelial cell homeostasis . This endothelial-specific expression pattern could explain the observed selectivity in cellular targeting.
What are the optimal methods for recombinant VEGI production and purification?
According to published research, recombinant human VEGI-192 has been successfully produced using the following methodology:
The specific procedure involved:
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Expression of recombinant human VEGI-192 in E. coli
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Purification to apparent homogeneity
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Quality control to ensure biological activity
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Preparation for various administration routes (i.p., i.v., or s.c.)
This approach has yielded VEGI-192 with sufficient purity and activity for in vivo studies, suggesting it represents an effective methodology for researchers studying this protein.
How can researchers measure VEGI activity in experimental contexts?
Several approaches for measuring VEGI activity have been validated in research settings:
These methodologies provide complementary information about both the efficacy and mechanism of VEGI activity, enabling comprehensive evaluation of this protein's biological functions.
What are the key controls required in VEGI/TNFSF15 functional studies?
When designing rigorous experiments to evaluate VEGI function, researchers should incorporate several critical controls:
What challenges exist in translating VEGI research from animal models to human applications?
Translating VEGI research from preclinical models to human applications faces several challenges:
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Species-specific differences: Human and murine VEGI might have different potency or receptor binding characteristics
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Delivery and stability: As a protein therapeutic, VEGI faces challenges related to in vivo stability, tissue penetration, and maintaining bioactivity
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Target population identification: Determining which patient populations might benefit most from VEGI-based therapies
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Biomarker development: Need for reliable biomarkers to monitor VEGI activity and treatment response
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Combination approaches: Understanding how VEGI might interact with other therapeutic modalities
While VEGI-192 showed no liver or kidney toxicity in mouse models , human-specific toxicities might emerge in clinical translation, necessitating careful safety assessment in early-phase trials.
How should researchers interpret seemingly contradictory data about VEGI function?
VEGI/TNFSF15 exhibits context-dependent functions that may appear contradictory, such as inhibiting endothelial cells while promoting haematopoietic stem cell expansion . When analyzing apparently contradictory results, researchers should consider:
| Observation | Potential Interpretation | Investigation Approach |
|---|---|---|
| Different effects on distinct cell types | Cell type-specific receptor expression or signaling | Comparative receptor profiling across cell types |
| Variation in efficacy across disease models | Model-specific vascular biology or accessibility | Pharmacokinetic/pharmacodynamic studies in multiple models |
| Concentration-dependent effects | Receptor saturation or activation of different pathways at varying concentrations | Detailed dose-response studies with pathway analysis |
| In vitro vs. in vivo discrepancies | Microenvironmental factors missing in simplified systems | Development of more complex in vitro models that better recapitulate in vivo conditions |
Understanding the biological context is crucial for proper interpretation of VEGI's multifaceted activities. The dual roles in angiogenesis inhibition and stem cell biology suggest sophisticated regulation of this protein's functions .
What statistical approaches are recommended for analyzing VEGI activity data?
While the search results don't provide specific statistical guidance for VEGI research, standard approaches for similar biological studies include:
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For tumor growth studies: Repeated measures ANOVA to account for longitudinal measurements of tumor volume over time
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For survival analysis: Kaplan-Meier curves with log-rank tests for comparing survival between treatment groups
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For vascular composition analysis: Appropriate parametric or non-parametric tests for comparing endothelial cell/smooth muscle cell ratios
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For dose-response studies: Regression models to establish dose-dependency
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For combination therapy assessment: Factorial design analysis to identify potential synergistic or antagonistic interactions
Power analysis should be conducted prior to experiments to ensure adequate sample sizes for detecting biologically meaningful effects with statistical confidence.
What are the emerging research areas for VEGI/TNFSF15 in human disease?
Based on current understanding of VEGI/TNFSF15 biology, several promising research directions emerge:
The unique ability of VEGI to eliminate tumor endothelial cells while preserving vascular smooth muscle cells and basement membrane suggests potential for developing therapies with reduced toxicity compared to less selective anti-angiogenic approaches.
How might VEGI research intersect with other fields like immunotherapy?
VEGI/TNFSF15 research has potential intersections with multiple fields:
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Immunotherapy: As a TNF superfamily member, VEGI may influence immune responses within the tumor microenvironment, potentially complementing checkpoint inhibitors or adoptive cell therapies
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Regenerative medicine: VEGI's role in haematopoietic stem cell biology suggests applications in tissue engineering and regeneration
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Bioengineering: Development of VEGI-based biomaterials for controlled vascularization in tissue constructs
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Umbilical cord blood banking: TNFSF15's ability to facilitate umbilical cord blood HSC expansion has implications for improving cord blood transplantation outcomes
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Precision medicine: Identifying biomarkers that predict response to VEGI-based therapeutics
These intersections represent opportunities for collaborative research across disciplines to fully realize the therapeutic potential of VEGI/TNFSF15.
Product Science Overview
Human Vascular Endothelial Growth Inhibitor (VEGI) is a protein that plays a crucial role in regulating angiogenesis, the process through which new blood vessels form from pre-existing vessels. Angiogenesis is essential for various physiological processes, including wound healing and embryonic development, but it also plays a significant role in the progression of diseases such as cancer. Recombinant technology allows for the production of VEGI in a laboratory setting, enabling researchers to study its functions and potential therapeutic applications.
VEGI belongs to the tumor necrosis factor (TNF) superfamily and is known for its ability to inhibit the proliferation of endothelial cells, which line the interior surface of blood vessels. By binding to specific receptors on these cells, VEGI can induce apoptosis (programmed cell death) and inhibit angiogenesis. This makes it a potential candidate for anti-cancer therapies, as it can starve tumors of the blood supply they need to grow and metastasize.
Recombinant VEGI is produced using genetic engineering techniques. The gene encoding VEGI is inserted into an expression vector, which is then introduced into a host cell, such as bacteria or yeast. These host cells are cultured under conditions that promote the expression of the VEGI protein, which can then be purified for research or therapeutic use.
One of the most promising applications of recombinant VEGI is in cancer therapy. By inhibiting angiogenesis, VEGI can potentially reduce tumor growth and spread. Studies have shown that combining VEGI with other treatments, such as immune checkpoint inhibitors, can enhance its anti-tumor effects . For example, a study involving elderly patients with non-small cell lung cancer (NSCLC) demonstrated that combining recombinant VEGI with anti-PD-1 therapy improved progression-free survival and overall survival .
Despite its potential, there are several challenges associated with the use of recombinant VEGI. One of the main issues is the potential for toxicity, as inhibiting angiogenesis can also affect normal physiological processes. Additionally, the production of recombinant proteins can be complex and costly. Future research is focused on improving the efficacy and safety of VEGI-based therapies, as well as developing more efficient production methods .
