Vascular Endothelial Growth Factor (VEGF) is a critical signaling protein involved in both vasculogenesis (the formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature) . VEGF plays a significant role in various physiological and pathological processes, including embryonic development, wound healing, and tumor growth .
The VEGF family consists of several members, including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placental growth factor (PlGF) . Among these, VEGF-A, commonly referred to as VEGF, is the most studied and is known for its potent angiogenic properties . VEGF-A binds to VEGF receptors (VEGFR-1 and VEGFR-2) on the surface of endothelial cells, initiating a cascade of signaling pathways that promote endothelial cell proliferation, migration, and new blood vessel formation .
Recombinant human VEGF (rhVEGF) is produced using various expression systems, including bacteria (E. coli), yeast (Pichia pastoris, Kluyveromyces lactis), and mammalian cells . Yeast expression systems, such as Kluyveromyces lactis, are particularly advantageous due to their ability to perform post-translational modifications and secrete the protein directly into the culture medium .
In the context of yeast-derived recombinant VEGF, Kluyveromyces lactis has been successfully used to express biologically active rhVEGF165 . The gene encoding human VEGF165 is cloned into the yeast genome, and the protein is secreted into the culture medium. The secreted rhVEGF165 is then purified using techniques such as ammonium sulfate precipitation and affinity chromatography .
The biological activity of yeast-derived rhVEGF165 has been confirmed through various assays. For instance, the proliferation assay on human umbilical vein endothelial cells (HUVEC) demonstrated that the yeast-derived rhVEGF165 exhibited proliferative activity in a dose- and time-dependent manner . Additionally, cell migration analysis via scratch assays indicated the potential of rhVEGF165 in promoting wound healing .
Recombinant VEGF has numerous therapeutic applications, particularly in the field of regenerative medicine. It is used to promote angiogenesis in ischemic tissues, enhance wound healing, and support tissue engineering efforts . Moreover, VEGF inhibitors are employed in cancer therapy to inhibit tumor angiogenesis and metastasis .