positive regulation of vascular endothelial growth factor production

Definition

Target type: biologicalprocess

Any process that increases or activates the frequency, rate, or extent of production of vascular endothelial growth factor. [GOC:BHF, GOC:rl]

Positive regulation of vascular endothelial growth factor (VEGF) production is a complex biological process that involves a intricate interplay of signaling pathways, transcription factors, and regulatory molecules. It is essential for proper vascular development, angiogenesis (the formation of new blood vessels), and wound healing. Here's a detailed description of this process:

**1. Stimulus Recognition and Signal Transduction:**
* **Hypoxia:** A decrease in oxygen levels (hypoxia) is a primary trigger for VEGF production. Hypoxia-inducible factor (HIF) is a transcription factor that is activated under hypoxic conditions.
* **Growth Factors:** Growth factors like platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) can also stimulate VEGF production. These factors bind to their respective receptors, initiating intracellular signaling cascades.
* **Cytokines:** Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1), can also contribute to VEGF upregulation.

**2. Signaling Pathways:**
* **HIF Pathway:** Hypoxia activates HIF-1α, which dimerizes with HIF-1β and translocates to the nucleus. The HIF complex binds to hypoxia-responsive elements (HREs) in the promoter region of VEGF gene, promoting its transcription.
* **MAPK Pathway:** Mitogen-activated protein kinase (MAPK) signaling pathways, activated by growth factors, can lead to the phosphorylation and activation of transcription factors like Elk-1, which can further enhance VEGF expression.
* **PI3K/AKT Pathway:** Phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) signaling pathways are also involved in VEGF upregulation. AKT can phosphorylate and inactivate the forkhead transcription factor (FOXO), preventing it from suppressing VEGF expression.

**3. Transcriptional Regulation:**
* **VEGF Gene Transcription:** The VEGF gene contains several regulatory elements that respond to various signals. HIF, Elk-1, and other transcription factors bind to these elements, stimulating the transcription of VEGF mRNA.
* **Post-Transcriptional Regulation:** MicroRNAs (miRNAs) can also regulate VEGF expression by targeting its mRNA for degradation or translation inhibition.

**4. VEGF Protein Production and Secretion:**
* **Translation:** The VEGF mRNA is translated into VEGF protein by ribosomes.
* **Post-Translational Modifications:** VEGF undergoes post-translational modifications, such as glycosylation, which are essential for its proper folding, stability, and biological activity.
* **Secretion:** Once processed, VEGF is secreted from the cell and interacts with its receptors on target cells, initiating angiogenesis and other physiological processes.

**5. VEGF Receptor Signaling:**
* **VEGF Receptors:** VEGF binds to its receptors, VEGFR-1 (Flt-1) and VEGFR-2 (KDR), which are tyrosine kinase receptors expressed on endothelial cells.
* **Signal Transduction:** Upon VEGF binding, these receptors undergo dimerization and autophosphorylation, activating downstream signaling pathways.
* **Angiogenesis:** The activation of VEGFR-2 leads to the proliferation, migration, and survival of endothelial cells, ultimately promoting the formation of new blood vessels.

**In summary:** Positive regulation of VEGF production involves a complex network of signaling pathways, transcription factors, and regulatory molecules. It is tightly controlled by various stimuli, including hypoxia, growth factors, and cytokines, and is essential for vascular development, angiogenesis, and wound healing. Dysregulation of this process can contribute to various diseases, including cancer and diabetic retinopathy.
'"

Proteins (18)

Compounds (663)