Recombinant human VEGF 165 protein (Qk048)

Protein background

Vascular endothelial growth factor (VEGF) is a member of the platelet-derived growth factor (PDGF) family and a core regulator of angiogenesis and vascular permeability [1,2]. It is responsible for the survival, proliferation, migration, and specialization of endothelial cells, thus called an endothelial cell surviving factor [2,3].

In humans, VEGF is produced as multiple alternately spliced isoforms indicating the number of amino acids in length: VEGF121, VEGF145, VEGF148, VEGF162, VEGF165a, VEGF165b, VEGF183, VEGF189, and VEGF206. VEGF165 (or VEGF165a) is the most abundantly expressed isoform composed of 165 amino acids [1].

VEGF165 signals through the type I transmembrane receptor tyrosine kinases VEGFR1 (also called Flt-1) and VEGFR2 (Flk-1/KDR) [2]. Some VEGF family members (including VEGFA 165) also bind to the co-receptors neuropilin 1 (NRP1) and neuropilin 2 (NRP2), which can stimulate VEGFR2 activation. It is characterized by the presence of eight conserved cysteine residues forming a receptor-binding cystine-knot structure [4,5].

VEGF is widely used in culturing primary endothelial cells, such as human umbilical vein endothelial cells, under serum-free conditions for blood vessel developmental studies. VEGF165 is commonly used with human-induced pluripotent stem cells or embryonic stem cells-derived endothelial cells for developing human vascular tissue models for disease mechanism studies. Immunocytochemical staining with CD31 expression marker is used to indicate the presence of endothelial cells, thereby suggesting successful endothelial cell differentiation [6,7]. Endothelial cells can also be derived from hair follicle stem cells [8].

In addition to its angiogenic role, it is also involved in promoting neurogenesis and stimulating neural stem cell proliferation [9,10]. It can promote the proliferation, survival or migration of other glial cells such as oligodendrocyte precursor cells, Schwann cells, and can stimulate the expression of trophic factors by astrocytes [11]. Moreover, it is a critical factor in generating human pluripotent stem cell-derived vascularized brain organoids [6].

Finally, VEGF also plays a role in bone formation and regulates mesenchymal stem cell differentiation of pluripotent stem cells and bone marrow stem cells [12,13]. Therefore, it serves as a survival factor for chondrocytes, hematopoietic stem cells, and tumor cells [12,14].

The strong implications of VEGF have led to preclinical studies on the potential of VEGF administration in neurodegenerative and ischemic diseases [1,2,11]. The inhibition of VEGF has been approved for the treatment of neovascular ocular disease to prevent the blood brain barrier breakdown or excessive angiogenesis11. It is also a target in anti-angiogenic strategies in cancer due to its contribution in tumor angiogenesis [2,14].