GO:1905562 regulation of vascular endothelial cell proliferation: Signaling Mechanisms, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1905562 describes any biological process that modulates the frequency, rate, or extent of vascular endothelial cell proliferation, a critical control point in angiogenesis and vascular homeostasis.
• Dysregulation of this process contributes to diabetic vascular injury, tumor angiogenesis, and developmental vascular defects.
• Key molecular regulators include WWP2, DDX3X, QKI-7, Piezo1, NOTCH receptors, and CD34, which act through ubiquitination, RNA stability, mechanotransduction, and cell-cell signaling.
• Metabolic cues such as nutrient availability and pregnancy-associated factors like PSG1 also influence endothelial proliferation.
• Experimental models for studying GO:1905562 include endothelial cell-specific knockout, point-mutation knock-in, and overexpression of candidate genes, combined with proliferation assays and transcriptomics.
• Understanding this GO term aids in identifying therapeutic targets for diabetes-related vascular complications, cancer, and pregnancy-associated vascular disorders.
Description
Regulation of vascular endothelial cell proliferation (GO:1905562) encompasses any process that modulates the frequency, rate, or extent of vascular endothelial cell proliferation. Vascular endothelial cells form the inner lining of blood vessels and their controlled proliferation is essential for angiogenesis, vascular repair, and maintenance of tissue perfusion. This GO term is therefore central to understanding how new blood vessels form during development and in pathological conditions such as diabetes, cancer, and ischemia. Researchers study GO:1905562 to identify molecular switches that can be targeted to promote or inhibit endothelial growth. For example, down-regulation of WWP2 aggravates type 2 diabetes mellitus-induced vascular endothelial injury by modulating ubiquitination and degradation of DDX3X. Similarly, QKI-7 degrades endothelial functional genes and regulates proliferation of diabetic vascular endothelial cells. These findings highlight the term's relevance to metabolic and cardiovascular diseases.
regulation of vascular endothelial cell proliferation At A Glance
| GO ID | GO:1905562 |
|---|---|
| GO term | regulation of vascular endothelial cell proliferation |
| Ontology | biological_process |
| Synonym | none |
| Major function | Modulates the frequency, rate, or extent of vascular endothelial cell proliferation |
| Related processes | Angiogenesis, vascular development, wound healing, tumor vascularization |
| Key regulators | WWP2, DDX3X, QKI-7, Piezo1, NOTCH, CD34, PSG1 |
| Disease relevance | Diabetic vascular injury, cancer, pregnancy complications, developmental vascular defects |
What Is GO:1905562?
According to the Gene Ontology, GO:1905562 is defined as any process that modulates the frequency, rate or extent of vascular endothelial cell proliferation. In other words, it includes all molecular events that either stimulate or inhibit the division of endothelial cells that line blood vessels. This regulation can occur through secreted factors, cell surface receptors, intracellular signaling cascades, and gene expression changes.
Why Is regulation of vascular endothelial cell proliferation Important in Cell Biology?
GO:1905562 is important because vascular endothelial cell proliferation is a fundamental process in both normal physiology and disease. During development, it drives the formation of the vascular network. In adults, it is required for wound healing and tissue regeneration. However, excessive endothelial proliferation contributes to tumor angiogenesis and inflammatory disorders, while insufficient proliferation leads to vascular rarefaction and ischemia. Understanding the regulation of this process can reveal therapeutic targets for diabetes, cancer, and cardiovascular diseases.
• Controls angiogenesis during embryonic development and tissue repair.
• Dysregulation leads to diabetic vascular complications, including endothelial injury.
• Plays a role in tumor progression by supporting tumor angiogenesis.
• Influenced by metabolic cues such as nutrient availability.
• Regulated by mechanotransduction via Piezo1 in brain vascular development.
• Modulated by NOTCH signaling to maintain endothelial phenotype.
• Affected by immune cell interactions, e.g., primary monocytes.
• CD34 expression on endothelial cells influences immune cell responses.
• Pregnancy-specific factors like PSG1 regulate vascular endothelial function.
• Provides targets for therapeutic intervention in vascular diseases.
What Happens During regulation of vascular endothelial cell proliferation?
Initiation by Growth Factors and Mechanical Cues
In simple terms: Endothelial cells start to divide when they receive signals from growth factors or when they sense changes in blood flow.
Vascular endothelial cell proliferation is initiated by a variety of extracellular signals, including growth factors, cytokines, and mechanical forces. For instance, Piezo1, a mechanosensitive ion channel, mediates the regulation of pericyte proliferation by blood flow during brain vascular development, indirectly influencing endothelial proliferation. Nutrient availability also regulates tumor and vascular endothelial cell proliferation, linking metabolism to cell cycle entry. Additionally, primary monocytes can regulate endothelial cell proliferation through secreted factors.
Intracellular Signaling and Gene Expression Changes
In simple terms: Once triggered, signals inside the cell turn genes on or off to control the cell cycle.
Upon stimulation, intracellular signaling cascades activate transcription factors that drive cell cycle progression. NOTCH signaling is a key regulator of endothelial cell phenotype, including proliferation, by modulating gene expression. QKI-7, an RNA-binding protein, degrades endothelial functional genes and thereby regulates proliferation of diabetic vascular endothelial cells. Similarly, WWP2, an E3 ubiquitin ligase, modulates ubiquitination and degradation of DDX3X, affecting vascular endothelial injury in type 2 diabetes.
Modulation by Immune and Pregnancy-Related Factors
In simple terms: Immune cells and pregnancy-related molecules can also influence how fast endothelial cells grow.
The immune microenvironment contributes to the regulation of endothelial proliferation. Primary monocytes have been shown to regulate endothelial cell proliferation, suggesting a role for immune-endothelial crosstalk. CD34 expression on endothelial cells is involved in the regulation of immune cell responses in vitro, which may indirectly affect proliferation. During pregnancy, pregnancy-specific beta-1-glycoprotein 1 (PSG1)-enriched exosomes are involved in the regulation of vascular endothelial cell function, including proliferation.
Integration of Pro- and Anti-Proliferative Signals
In simple terms: The final decision to divide depends on a balance between signals that promote and inhibit growth.
Endothelial cell proliferation is tightly controlled by the integration of pro-proliferative and anti-proliferative signals. For example, NOTCH signaling can either promote or inhibit proliferation depending on context. Nutrient stress can suppress proliferation, as observed in tumor and vascular endothelial cells. Dysregulation of this balance, such as through WWP2 down-regulation, can lead to vascular injury in diabetes. Thus, GO:1905562 encompasses the dynamic modulation of these opposing inputs.
Key Genes Involved in GO:1905562 regulation of vascular endothelial cell proliferation
The following genes and proteins have been experimentally implicated in the regulation of vascular endothelial cell proliferation (GO:1905562).
| Gene | Major Role | Research Relevance |
|---|---|---|
| WWP2 | E3 ubiquitin ligase that ubiquitinates DDX3X | Down-regulation aggravates diabetes-induced vascular endothelial injury |
| DDX3X | RNA helicase involved in RNA metabolism | Target of WWP2-mediated ubiquitination in endothelial injury |
| Piezo1 | Mechanosensitive ion channel | Regulates pericyte proliferation by blood flow in brain vascular development |
| QKI-7 | RNA-binding protein that degrades endothelial functional genes | Regulates proliferation of diabetic vascular endothelial cells |
| NOTCH1 | Transmembrane receptor in cell-cell signaling | Regulates endothelial cell phenotype including proliferation |
| NOTCH4 | Transmembrane receptor in cell-cell signaling | Regulates endothelial cell phenotype including proliferation |
| CD34 | Cell surface sialomucin | Endothelial CD34 expression and regulation of immune cell response |
| PSG1 | Pregnancy-specific glycoprotein | Enriched in exosomes involved in regulation of vascular endothelial function |
| Monocyte-derived factors | Secreted cytokines and growth factors | Primary monocytes regulate endothelial cell proliferation |
| Nutrient-sensing pathways | Metabolic regulators | Nutrient regulation of tumor and vascular endothelial cell proliferation |
| VEGFA | Growth factor | Indirectly implicated through general angiogenesis literature |
| FGF2 | Growth factor | Indirectly implicated through general angiogenesis literature |
| HIF1A | Transcription factor | Indirectly implicated through nutrient regulation |
| mTOR | Kinase in nutrient signaling | Indirectly implicated through nutrient regulation |
| AMPK | Energy sensor kinase | Indirectly implicated through nutrient regulation |
| CDKN1A | Cell cycle inhibitor | Indirectly implicated through general proliferation control |
| MYC | Transcription factor | Indirectly implicated through general proliferation control |
| CCND1 | Cyclin D1 | Indirectly implicated through general proliferation control |
How Is regulation of vascular endothelial cell proliferation Regulated?
The regulation of vascular endothelial cell proliferation (GO:1905562) is itself controlled by multiple upstream mechanisms. Nutrient availability, such as glucose and amino acids, can modulate proliferation through metabolic signaling pathways. Mechanical forces from blood flow act via Piezo1 to influence pericyte and endothelial proliferation during brain vascular development. NOTCH signaling provides context-dependent regulation of endothelial phenotype. Immune cells, including primary monocytes, secrete factors that regulate endothelial proliferation. In diabetes, down-regulation of WWP2 leads to DDX3X accumulation and vascular endothelial injury, illustrating post-translational control. QKI-7 degrades endothelial functional genes, thereby affecting proliferation in diabetic conditions. Pregnancy-related exosomes carrying PSG1 also regulate endothelial function.
regulation of vascular endothelial cell proliferation and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| WWP2 | Type 2 diabetes mellitus-induced vascular endothelial injury | Endothelial cell-specific WWP2 knockout mice |
| QKI-7 | Diabetic vascular endothelial cell proliferation | QKI-7 overexpression in human endothelial cells |
| Piezo1 | Brain vascular development defects | Piezo1 knockout zebrafish or mice |
| NOTCH1 | Vascular anomalies and cancer | NOTCH1 knockout endothelial cells |
| PSG1 | Pregnancy-related vascular disorders | PSG1-enriched exosome treatment in endothelial cells |
Diabetic Vascular Injury
Type 2 diabetes mellitus induces vascular endothelial injury, and down-regulation of WWP2 aggravates this process by modulating ubiquitination and degradation of DDX3X. QKI-7 also regulates proliferation of diabetic vascular endothelial cells by degrading endothelial functional genes. These findings link GO:1905562 to diabetic vascular complications.
Cancer and Tumor Angiogenesis
Nutrient regulation of tumor and vascular endothelial cell proliferation is critical for tumor angiogenesis. Endothelial proliferation supports the growth of new blood vessels that supply tumors, making GO:1905562 a potential target for anti-angiogenic therapy.
Developmental Vascular Defects
Piezo1-dependent regulation of pericyte proliferation by blood flow is essential for brain vascular development. Disruption of this mechanotransduction pathway can lead to vascular malformations, highlighting the importance of GO:1905562 in development.
Pregnancy-Related Vascular Disorders
Pregnancy-specific beta-1-glycoprotein 1 (PSG1)-enriched exosomes are involved in the regulation of vascular endothelial cell function during pregnancy. Dysregulation of this process may contribute to pregnancy complications such as preeclampsia.
From regulation of vascular endothelial cell proliferation-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does WWP2 regulate endothelial proliferation in diabetes? | Endothelial-specific WWP2 knockout mouse |
| How does QKI-7 affect diabetic endothelial proliferation? | QKI-7 overexpression and knockdown in human endothelial cells |
| What is the role of Piezo1 in brain vascular development? | Piezo1 knockout zebrafish |
| How does NOTCH signaling modulate endothelial phenotype? | NOTCH1/4 knockout or knock-in endothelial cells |
| Do monocytes regulate endothelial proliferation? | Co-culture of primary monocytes with endothelial cells |
| What is the effect of PSG1 exosomes on endothelial function? | PSG1-enriched exosome treatment in endothelial cells |
How to Study the regulation of vascular endothelial cell proliferation Process
| Method | What It Measures | Typical Application |
|---|---|---|
| EdU incorporation | DNA synthesis | Quantify endothelial proliferation |
| RNA-seq | Global gene expression | Identify pathways regulating proliferation |
| Proteomics | Protein abundance and modifications | Study ubiquitination of DDX3X by WWP2 |
| Calcium imaging | Intracellular calcium levels | Assess Piezo1 mechanotransduction |
| Co-culture assays | Cell-cell interactions | Study monocyte-endothelial crosstalk |
| Exosome treatment | Functional effects of exosomes | Test PSG1-enriched exosomes on endothelial cells |
| Immunofluorescence | Protein localization and expression | Detect CD34 and NOTCH in endothelial cells |
| Western blot | Protein expression and phosphorylation | Validate signaling changes |
Proliferation Assays
EdU incorporation, BrdU labeling, and MTT assays are commonly used to measure vascular endothelial cell proliferation. These methods quantify DNA synthesis and metabolic activity, providing direct readouts of GO:1905562 activity.
Transcriptomics and RNA Sequencing
RNA-seq can identify gene expression changes associated with altered endothelial proliferation. For example, QKI-7-mediated degradation of endothelial functional genes was studied using transcriptomic approaches.
Proteomics and Ubiquitination Analysis
Mass spectrometry-based proteomics and ubiquitination assays can reveal post-translational modifications. WWP2-mediated ubiquitination of DDX3X was characterized using such methods.
Imaging and Mechanotransduction Studies
Live-cell imaging and calcium imaging can assess Piezo1 activity and its effects on proliferation. These techniques were used to study blood flow-dependent pericyte proliferation in brain vascular development.
How CRISPR Can Be Used to Study GO:1905562 regulation of vascular endothelial cell proliferation
Knockout
CRISPR knockout of genes such as WWP2, QKI-7, or Piezo1 in endothelial cells or animal models can reveal their causal roles in regulating vascular endothelial cell proliferation. For example, WWP2 knockout would test whether loss of this E3 ligase aggravates diabetic vascular injury.
Point Mutation
Introducing point mutations in genes like Piezo1 can dissect mechanotransduction domains required for proliferation regulation. Such mutations can mimic human variants associated with vascular disorders.
Knock-in
Knock-in of tagged versions of NOTCH receptors or CD34 can enable live-cell imaging and biochemical tracking of their role in endothelial proliferation.
Overexpression
Overexpression of QKI-7 or PSG1 in endothelial cells can model gain-of-function states and assess effects on proliferation. This approach is useful for studying diabetic or pregnancy-related vascular dysfunction.
How EDITGENE Supports regulation of vascular endothelial cell proliferation Research
Researchers studying regulation of vascular endothelial cell proliferation-related genes often need to determine whether a candidate gene is causally involved in endothelial growth control. EDITGENE provides CRISPR-based cell model services to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for regulation of vascular endothelial cell proliferation research.
Frequently Asked Questions About regulation of vascular endothelial cell proliferation
What is GO:1905562?
GO:1905562 is the Gene Ontology term for regulation of vascular endothelial cell proliferation, defined as any process that modulates the frequency, rate or extent of vascular endothelial cell proliferation.
What genes are involved in regulation of vascular endothelial cell proliferation?
Key genes include WWP2, DDX3X, QKI-7, Piezo1, NOTCH1, NOTCH4, CD34, and PSG1, as shown in recent studies.
How is vascular endothelial cell proliferation regulated in diabetes?
In diabetes, down-regulation of WWP2 leads to DDX3X accumulation and endothelial injury, while QKI-7 degrades endothelial functional genes, affecting proliferation.
What role does Piezo1 play in vascular endothelial cell proliferation?
Piezo1 mediates mechanotransduction from blood flow to regulate pericyte proliferation during brain vascular development, indirectly influencing endothelial proliferation.
How does NOTCH signaling regulate endothelial cell proliferation?
NOTCH signaling modulates endothelial cell phenotype, including proliferation, through cell-cell communication and gene expression changes.
Can monocytes regulate vascular endothelial cell proliferation?
Yes, primary monocytes have been shown to regulate endothelial cell proliferation through secreted factors.
What is the link between CD34 and endothelial proliferation?
CD34 expression on endothelial cells is involved in the regulation of immune cell responses, which may indirectly affect proliferation.
How do pregnancy-specific factors affect endothelial proliferation?
PSG1-enriched exosomes are involved in the regulation of vascular endothelial cell function during pregnancy, including proliferation.
What experimental models are used to study GO:1905562?
Common models include endothelial cell-specific knockout mice, overexpression cell lines, and co-culture systems with immune cells.
Why is regulation of vascular endothelial cell proliferation important for cancer?
Nutrient regulation of tumor and vascular endothelial cell proliferation supports tumor angiogenesis, making it a target for anti-angiogenic therapy.
Conclusion
GO:1905562, regulation of vascular endothelial cell proliferation, is a critical biological process with broad implications for development, metabolism, and disease. Key regulators such as WWP2, QKI-7, Piezo1, and NOTCH signaling pathways have been identified through recent research. Understanding this process offers opportunities for therapeutic intervention in diabetes, cancer, and pregnancy-related vascular disorders. Continued research using CRISPR models and multi-omics approaches will further elucidate the molecular mechanisms governing endothelial proliferation.
References
- 1. You S et al.. 2023. Down-regulation of WWP2 aggravates Type 2 diabetes mellitus-induced vascular endothelial injury through modulating ubiquitination and degradation of DDX3X.. Cardiovasc Diabetol 22(1):107 PMID: 37149668
- 2. Zi H et al.. 2024. Piezo1-dependent regulation of pericyte proliferation by blood flow during brain vascular development.. Cell Rep 43(1):113652 PMID: 38175750
- 3. Enciso JM et al.. 2007. Nutrient regulation of tumor and vascular endothelial cell proliferation.. Curr Cancer Drug Targets 7(5):432-7 PMID: 17691902
- 4. Xu J et al.. 2022. Regulation of the Proliferation of Diabetic Vascular Endothelial Cells by Degrading Endothelial Cell Functional Genes with QKI-7.. Contrast Media Mol Imaging 2022:6177809 PMID: 35711530
- 5. Mack JJ et al.. 2018. NOTCH regulation of the endothelial cell phenotype.. Curr Opin Hematol 25(3):212-218 PMID: 29547401
- 6. Schubert SY et al.. 2008. Regulation of endothelial cell proliferation by primary monocytes.. Arterioscler Thromb Vasc Biol 28(1):97-104 PMID: 17991870
- 7. Arakelian L et al.. 2023. Endothelial CD34 expression and regulation of immune cell response in-vitro.. Sci Rep 13(1):13512 PMID: 37598252
- 8. Jia L et al.. 2023. Pregnancy-specific beta-1-glycoprotein 1-enriched exosomes are involved in the regulation of vascular endothelial cell function during pregnancy.. Placenta 139:138-147 PMID: 37392715
