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VEGF


Official Full Name
vascular endothelial growth factor A
Organism
Homo sapiens
Gene ID
7422
Background
This gene is a member of the PDGF/VEGF growth factor family. It encodes a heparin-binding protein, which exists as a disulfide-linked homodimer. This growth factor induces proliferation and migration of vascular endothelial cells, and is essential for both physiological and pathological angiogenesis. Disruption of this gene in mice resulted in abnormal embryonic blood vessel formation. This gene is upregulated in many known tumors and its expression is correlated with tumor stage and progression. Elevated levels of this protein are found in patients with POEMS syndrome, also known as Crow-Fukase syndrome. Allelic variants of this gene have been associated with microvascular complications of diabetes 1 (MVCD1) and atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been described. There is also evidence for alternative translation initiation from upstream non-AUG (CUG) codons resulting in additional isoforms. A recent study showed that a C-terminally extended isoform is produced by use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism, and that this isoform is antiangiogenic. Expression of some isoforms derived from the AUG start codon is regulated by a small upstream open reading frame, which is located within an internal ribosome entry site. The levels of VEGF are increased during infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus promoting inflammation by facilitating recruitment of inflammatory cells, and by increasing the level of angiopoietin II (Ang II), one of two products of the SARS-CoV-2 binding target, angiotensin-converting enzyme 2 (ACE2). In turn, Ang II facilitates the elevation of VEGF, thus forming a vicious cycle in the release of inflammatory cytokines. [provided by RefSeq, Jun 2020]
Synonyms
VPF; VEGF; MVCD1; L-VEGF
Bio Chemical Class
Growth factor
Protein Sequence
MNFLLSWVHWSLALLLYLHHAKWSQAAPMAEGGGQNHHEVVKFMDVYQRSYCHPIETLVDIFQEYPDEIEYIFKPSCVPLMRCGGCCNDEGLECVPTEESNITMQIMRIKPHQGQHIGEMSFLQHNKCECRPKKDRARQEKKSVRGKGKGQKRKRKKSRYKSWSVYVGARCCLMPWSLPGPHPCGPCSERRKHLFVQDPQTCKCSCKNTDSRCKARQLELNERTCRCDKPRR
Open
Disease
Bone growth disorder, Breast cancer, Circulatory system disease, Colorectal cancer, Corneal disease, Fallopian tube cancer, Fibrosis, Hypopharyngeal cancer, Liver cancer, Lung cancer, Lymphoma, Macular degeneration, Malignant haematopoietic neoplasm, Metabolic disorder, Metastatic tumour, Muscular atrophy, Nasopharyngeal cancer, Neurodegenerative disorder, Ovarian cancer, Peritoneal cancer, Retinopathy, Rheumatoid arthritis, Solid tumour/cancer, Stomach cancer, Transient ischaemic attack, Vascular system developmental anomaly, Virus infection
Approved Drug
5 +
Clinical Trial Drug
15 +
Discontinued Drug
2 +

Cat.No. Product Name Price
SHL125316 shRNA set against Mouse Vegfa(NM_001110268.1) Inquiry
SHL125280 shRNA set against Mouse Vegfa(NM_001025250.3) Inquiry
SHL122724 shRNA set against Rat Vegfa(NM_031836.2) Inquiry
SHH429864 shRNA set against Mouse TMEM191C (NM_177473.3) Inquiry
SHW011804 shRNA set against Danio rerio TMEM192 (NM_001102393) Inquiry
SHW005542 shRNA set against Chicken VEGFA (NM_205042) Inquiry
SHW002713 shRNA set against Chicken VEGFA (NM_001110355) Inquiry
SHL125182 shRNA set against Mouse Vegfa(NM_001110268.1) Inquiry
SHL122652 shRNA set against Mouse Vegfa(NM_001025257.3) Inquiry
SHL122368 shRNA set against Human VEGFA(NM_001171630.1) Inquiry
SHH442580 shRNA set against Rat VEGFA (NM_031836.2) Inquiry
SHH442572 shRNA set against Human VEGFA (NM_003376.5) Inquiry
SHH442568 shRNA set against Rat VEGF (NM_053653.1) Inquiry
SHH429880 shRNA set against Rat TMEM192 (NM_001014141.1) Inquiry
SHH429876 shRNA set against Mouse TMEM192 (NM_028427.3) Inquiry
SHH429872 shRNA set against Human TMEM192 (NM_001100389.1) Inquiry
SHW012025 shRNA set against Danio rerio VEGFAA (NM_001110349) Inquiry
SHW014867 shRNA set against Danio rerio VEGFAA (NM_131408) Inquiry
Cat.No. Product Name Price
CDCB156479 Rat VEGFA ORF clone (AY033506.1) Inquiry
CDFL013945 Mouse Tmem191c cDNA Clone(NM_177473.3) Inquiry
CDFH021068 Human VEGFA cDNA Clone(NM_001171630.1) Inquiry
CDFH021067 Human VEGFA cDNA Clone(NM_001171629.1) Inquiry
CDFH021066 Human VEGFA cDNA Clone(NM_001171628.1) Inquiry
CDFH021065 Human VEGFA cDNA Clone(NM_001171627.1) Inquiry
CDFH021064 Human VEGFA cDNA Clone(NM_001171626.1) Inquiry
CDFH021063 Human VEGFA cDNA Clone(NM_001171625.1) Inquiry
CDFH021062 Human VEGFA cDNA Clone(NM_001171623.1) Inquiry
CDFH021061 Human VEGFA cDNA Clone(NM_001171624.1) Inquiry
CDFH021060 Human VEGFA cDNA Clone(NM_001171622.1) Inquiry
CDFH019825 Human TMEM192 cDNA Clone(NM_001100389.1) Inquiry
CDFG018990 Mouse Vegfa cDNA Clone(NM_001110267.1) Inquiry
CDFG017967 Mouse Vegfa cDNA Clone(NM_001110268.1) Inquiry
CDFG017966 Mouse Vegfa cDNA Clone(NM_001110266.1) Inquiry
CDFG017513 Mouse Vegfa cDNA Clone(NM_001025257.3) Inquiry
CDFL013946 Mouse Tmem192 cDNA Clone(NM_028427.3) Inquiry
CDFL014824 Mouse Vegfa cDNA Clone(NM_009505.4) Inquiry
CDFR003269 Rat Tmem192 cDNA Clone(NM_001014141.1) Inquiry
CDFR009248 Rat Vegfa cDNA Clone(NM_001110333.1) Inquiry
MiUTR3H-02402 VEGFA miRNA 3'UTR clone Inquiry
MiUTR3H-02401 VEGFA miRNA 3'UTR clone Inquiry
MiUTR3H-02400 VEGFA miRNA 3'UTR clone Inquiry
MiUTR3H-02399 VEGFA miRNA 3'UTR clone Inquiry
MiUTR3H-02398 VEGFA miRNA 3'UTR clone Inquiry
MiUTR3H-02397 VEGFA miRNA 3'UTR clone Inquiry
MiUTR1R-06664 TMEM192 miRNA 3'UTR clone Inquiry
CDFG017462 Mouse Vegfa cDNA Clone(NM_001025250.3) Inquiry
MiUTR1M-12677 VEGFA miRNA 3'UTR clone Inquiry
MiUTR1M-12675 VEGFA miRNA 3'UTR clone Inquiry
MiUTR1M-12674 VEGFA miRNA 3'UTR clone Inquiry
MiUTR1H-11112 VEGFA miRNA 3'UTR clone Inquiry
CDFR012965 Rat Vegfa cDNA Clone(NM_031836.2) Inquiry
CDFR009251 Rat Vegfa cDNA Clone(NM_001110336.1) Inquiry
CDFR009250 Rat Vegfa cDNA Clone(NM_001110335.1) Inquiry
CDFR009249 Rat Vegfa cDNA Clone(NM_001110334.1) Inquiry
MiUTR1M-12676 VEGFA miRNA 3'UTR clone Inquiry
MiUTR3H-02403 VEGFA miRNA 3'UTR clone Inquiry
CDCS406704 Human VEGFA ORF Clone (BC065522) Inquiry
CDCL186715 Human VEGF ORF clone(NM_001171628.1) Inquiry
CDCB173500 Danio rerio VEGFAA ORF Clone (NM_001110349) Inquiry
CDCB176342 Danio rerio VEGFAA ORF Clone (NM_131408) Inquiry
CDCH099382 Mouse Vegfa ORF clone (NM_001110267.1) Inquiry
CDCH099384 Mouse Vegfa ORF clone (NM_001110266.1) Inquiry
CDCH099386 Mouse Vegfa ORF clone (NM_009505.4) Inquiry
CDCH099396 Mouse Vegfa ORF clone (NM_001025250.3) Inquiry
CDCL186717 Human VEGF ORF clone(NM_001171624.1) Inquiry
CDCL186720 Mouse VEGF-A ORF clone(NM_001025257.3) Inquiry
CDCR342479 Human VEGFA ORF Clone(NM_001025367.2) Inquiry
SKO0933 VEGFA Validated sgRNA vector Inquiry
CDCR356123 Human VEGFA ORF Clone(NM_001171627.1) Inquiry
CDCR356128 Human VEGFA ORF Clone(NM_001171629.1) Inquiry
CDCR376298 Rat Vegfa ORF Clone(NM_001110336.1) Inquiry
CDCR376297 Rat Vegfa ORF Clone(NM_001110335.1) Inquiry
CDCR356115 Human VEGFA ORF Clone(NM_001171623.1) Inquiry
CDCB156720 Danio rerio (zebrafish) VEGFAA ORF clone (NM_001110349.2) Inquiry
CDCB156950 Canine VEGFA ORF clone (AF133248.1) Inquiry
CDCB164188 Chicken VEGFA ORF Clone (NM_001110355) Inquiry
CDCB167017 Chicken VEGFA ORF Clone (NM_205042) Inquiry
CDCB173279 Danio rerio TMEM192 ORF Clone (NM_001102393) Inquiry
CDCB191470 Rabbit TMEM191C ORF clone (XM_002719722.2) Inquiry
CDCB191958 Rabbit TMEM192 ORF clone (XM_002720555.2) Inquiry
CDCH092392 human TMEM191C ORF clone (NM_001207052.1) Inquiry
CDCH092394 Mouse Tmem191c ORF clone (NM_177473.3) Inquiry
CDCH099380 Mouse Vegfa ORF clone (NM_001110268.1) Inquiry
CDCR347105 Human TMEM192 ORF Clone(NM_001100389.1) Inquiry
CDCR376296 Rat Vegfa ORF Clone(NM_001110334.1) Inquiry
CDCR376295 Rat Vegfa ORF Clone(NM_001110333.1) Inquiry
CDCR370275 Rat Tmem192 ORF Clone(NM_001014141.1) Inquiry
CDCR356129 Human VEGFA ORF Clone(NM_001171630.1) Inquiry
CDCR379979 Rat Vegfa ORF Clone(NM_031836.2) Inquiry
CDCL186716 Human VEGF ORF clone(NM_001171625.1) Inquiry
CDCL186719 Human VEGFA ORF clone(NM_001171626.1) Inquiry
CDCR240103 Mouse Tmem192 ORF Clone(NM_001163747.1) Inquiry
CDCR261459 Mouse Tmem192 ORF Clone(NM_028427.3) Inquiry
CDCR285351 Human VEGFA ORF Clone(NM_003376.5) Inquiry
CDCH099376 human VEGFA ORF clone (NM_001171622.1) Inquiry
CDCS407510 Human TMEM192 ORF Clone (BC036301) Inquiry

Detailed Information

Vascular Endothelial Growth Factor A (VEGFA) is located on human chromosome 6p21.3 and belongs to the PDGF/VEGF growth factor family. Its transcript undergoes complex alternative splicing, generating multiple isoforms, including VEGF121, VEGF145, VEGF165, VEGF183, VEGF189, and VEGF206. These isoforms differ significantly in receptor-binding specificity, heparin-binding capacity, and biological activity. VEGF165 is the most abundantly expressed isoform in most tissues, displaying full biological activity and high solubility. In contrast, VEGF189 and VEGF206 primarily bind to extracellular matrix components and cell-surface heparan sulfate proteoglycans, requiring proteolytic cleavage to release active forms. A distinct isoform, VEGF165b, can bind VEGFR2 without activating downstream signaling, exhibiting anti-angiogenic properties and contributing to an endogenous regulatory balance.

Figure 1. VEGF protein family.Figure 1. VEGF protein family. (Apte RS, et al., 2019)

VEGF protein is a secreted homodimeric glycoprotein with a molecular weight of approximately 40–45 kDa. Monomers are linked via disulfide bonds to form functional dimers. The molecule contains a characteristic cystine knot motif, a conserved structural domain among VEGF family members. Its expression is tightly regulated at multiple levels. Hypoxia-inducible factor (HIF) signaling plays a central role, where HIF-1α stabilization under low oxygen conditions leads to nuclear translocation, dimerization with HIF-1β, and activation of VEGF transcription via hypoxia response elements (HREs) in the promoter. In addition, inflammatory cytokines, growth factors, and oncogenes can upregulate VEGF expression through diverse signaling pathways. Post-transcriptional mechanisms, including mRNA stability, microRNA-mediated translational inhibition, and proteolytic processing, further fine-tune VEGF levels.

Biological Functions and Signaling Pathways

VEGF is a highly specific mitogen for endothelial cells and serves as a central regulator of both physiological and pathological angiogenesis. Its biological effects are primarily mediated through three receptor tyrosine kinases: VEGFR1 (Flt-1), VEGFR2 (KDR/Flk-1), and VEGFR3 (Flt-4), with VEGFR2 acting as the key receptor for promoting endothelial proliferation, migration, survival, and increased vascular permeability. VEGF binding induces receptor dimerization and autophosphorylation, activating multiple downstream signaling cascades, including the PLCγ-PKC-MAPK pathway for cell proliferation, the PI3K-Akt pathway for survival, and the FAK-paxillin pathway for migration. Functional VEGF receptors are also expressed on various tumor cells, where autocrine and paracrine VEGF signaling can directly enhance cell survival and invasiveness.

VEGF uniquely regulates vascular permeability, far exceeding classical inflammatory mediators like histamine. It promotes vesiculo-vacuolar organelle formation and intercellular gap opening, facilitating plasma protein extravasation. This process is physiologically important in early wound healing, providing a scaffold for fibrin deposition. In pathological conditions such as tumors, high vascular permeability contributes to elevated interstitial pressure, impeding drug delivery and promoting inflammatory infiltration. Beyond angiogenesis, VEGF modulates the immune microenvironment by inhibiting dendritic cell maturation, promoting regulatory T cell expansion, and recruiting myeloid-derived suppressor cells, creating an immunosuppressive milieu. In the nervous system, VEGF interacts with NRP1 to guide motor neuron axon navigation and cell body migration during embryonic development, especially for facial motor neurons migrating from rhombomere 4 to 6.

Recent findings highlight VEGF's role in maintaining tumor stem cell populations. Autocrine VEGF signaling via VEGFR2 upregulates stemness-associated transcription factors such as SOX2, OCT4, and NANOG, promoting cancer stem cell self-renewal and chemoresistance. This evidence expands the rationale for VEGF-targeted therapy, indicating direct effects on tumor cell stemness beyond vascular modulation. In severe viral infections, including SARS-CoV-2, VEGF upregulation contributes to inflammatory cell recruitment and amplifies vascular stress, exacerbating tissue injury.

Clinical Relevance and Targeted Therapy

VEGF is central to disease mechanisms, particularly in oncology and ophthalmology. Overexpression drives tumor progression, contributes to therapy resistance, and supports metastasis. In ocular diseases, VEGF plays a key role in diabetic macular edema and neovascular age-related macular degeneration by disrupting the blood-retinal barrier and promoting retinal edema. Current first-line therapies involve intravitreal injection of anti-VEGF agents, which require repeated dosing and can face challenges with patient adherence and diminishing long-term efficacy. Newer strategies, including bispecific antibodies and dual-target fusion proteins, aim to simultaneously inhibit angiogenesis and inflammation, addressing the complex pathological mechanisms.

Challenges and Future Directions

Anti-VEGF therapy faces limitations such as drug resistance, adverse effects, and administration challenges. Compensatory angiogenic pathways can emerge during tumor treatment, reducing efficacy, while a subset of ocular patients exhibit suboptimal responses due to non-VEGF-driven mechanisms. Systemic adverse events may include hypertension, proteinuria, and thromboembolic events, whereas intraocular injections carry risks of elevated intraocular pressure, retinal detachment, and endophthalmitis. Ongoing research seeks to optimize therapeutic strategies, improve delivery, and overcome resistance to enhance clinical outcomes.

1.Apte RS, Chen DS, Ferrara N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019 Mar 7;176(6):1248-1264.

Reference

  1. Carmeliet P. VEGF as a key mediator of angiogenesis in cancer. Oncology. 2005;69 Suppl 3:4-10.
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