regulation of vascular endothelial growth factor production

Definition

Target type: biologicalprocess

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

Vascular endothelial growth factor (VEGF) production is tightly regulated to ensure proper vascular development, maintenance, and repair. Multiple factors and pathways influence VEGF levels, including:

**Transcriptional Regulation:**

* **Hypoxia:** Low oxygen levels trigger the expression of hypoxia-inducible factor (HIF)-1α, a transcription factor that binds to hypoxia response elements (HREs) in the VEGF gene promoter, promoting VEGF transcription.
* **Growth factors and cytokines:** Platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), and tumor necrosis factor-α (TNF-α) can induce VEGF expression.
* **Other signaling pathways:** The Wnt/β-catenin, MAPK, and PI3K/Akt pathways can influence VEGF production by modulating transcription factor activity and gene expression.

**Post-Transcriptional Regulation:**

* **MicroRNAs:** Certain microRNAs (miRNAs) can bind to VEGF mRNA and repress its translation, reducing VEGF levels.
* **mRNA stability:** Factors like AU-rich elements (AREs) in the 3' untranslated region (UTR) of VEGF mRNA can affect its stability and influence translation.

**Post-Translational Regulation:**

* **Protein processing:** VEGF undergoes post-translational modifications, including proteolytic cleavage and glycosylation, which can affect its stability, activity, and interaction with receptors.
* **Protein degradation:** Proteasome-mediated degradation can regulate VEGF levels.

**Cellular Context and Tissue Specificity:**

* **Endothelial cells:** These cells are the primary target of VEGF and play a central role in angiogenesis.
* **Other cell types:** Cells like fibroblasts, smooth muscle cells, and tumor cells also produce VEGF, contributing to angiogenesis and other processes.

**Pathological Implications:**

* **Cancer:** Tumors often overexpress VEGF to promote angiogenesis and support tumor growth.
* **Diabetic retinopathy:** High glucose levels can induce VEGF production, leading to abnormal vessel growth and leakage in the eye.
* **Rheumatoid arthritis:** VEGF contributes to inflammation and joint damage in this autoimmune disease.

**Therapeutic Targeting:**

* **Anti-VEGF therapy:** Inhibiting VEGF production or blocking its receptor activity is a key strategy in treating various diseases, including cancer and age-related macular degeneration.'
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Proteins (2)

Compounds (21)