Vascular Endothelial Growth Inhibitor (VEGI), also known as Tumor Necrosis Factor Superfamily Member 15 (TNFSF15) or TNF-like ligand 1A (TL1A), is a potent anti-angiogenic cytokine. It plays a crucial role in inhibiting the formation of new blood vessels (angiogenesis), which is essential in various physiological and pathological processes, including cancer, inflammation, and wound healing .
The recombinant form of VEGI, particularly the human recombinant version with a His tag, is engineered to facilitate purification and detection. The His tag, typically a sequence of six histidine residues, allows for affinity purification using nickel or cobalt-based resins. This recombinant protein is expressed in host systems such as HEK293 cells, ensuring proper folding and post-translational modifications .
VEGI exerts its anti-angiogenic effects by binding to its receptor, Death Receptor 3 (DR3), on the surface of endothelial cells. This interaction triggers downstream signaling pathways that lead to apoptosis (programmed cell death) of endothelial cells, thereby inhibiting the formation of new blood vessels . This mechanism is particularly significant in the context of cancer, where inhibiting angiogenesis can starve tumors of the necessary blood supply for growth and metastasis.
VEGI has been implicated in various diseases characterized by abnormal angiogenesis. For instance, elevated levels of soluble TL1A (a form of VEGI) have been detected in the serum of patients with T-cell mediated autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis, and inflammatory bowel disease . These findings suggest that VEGI could be a potential therapeutic target for these conditions. Recent clinical studies have also indicated that anti-TL1A antibody treatment shows promise in managing inflammatory and autoimmune disorders .
The development of recombinant VEGI with a His tag has facilitated extensive research into its biological functions and therapeutic potential. The His tag allows for efficient purification and detection, enabling researchers to study the protein’s structure, function, and interactions in detail. This recombinant protein is also used in various assays to investigate its effects on endothelial cell proliferation, migration, and apoptosis .