Vascular endothelial growth inhibitor (VEGI), also known as TNF-like ligand 1A (TL1A) and TNF superfamily member 15 (TNFSF15), is protein that in humans is encoded by the TNFSF15gene. VEGI is an anti-angiogenic protein.[5] It belongs to tumor necrosis factor (ligand) superfamily, where it is member 15.[6] It is the sole known ligand for death receptor 3,[7] and it can also be recognized by decoy receptor 3.
The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is abundantly expressed in endothelial cells, but is not expressed in either B or T cells. The expression of this protein is inducible by TNF-alpha and IL-1 alpha. This cytokine is a ligand for receptor TNFRSF25 (death receptor 3) and TNFRSF6B (decoy receptor 3). It can activate both the NF-κB and MAPK signalling pathways, and acts as an autocrine factor to induce apoptosis in endothelial cells. This cytokine is also found to inhibit endothelial cell proliferation, and thus may function as an angiogenesis inhibitor. An additional isoform encoded by an alternatively spliced transcript variant has been reported but the sequence of this transcript has not been determined.[6]
Tan KB, Harrop J, Reddy M, Young P, Terrett J, Emery J, Moore G, Truneh A (Dec 1997). "Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells". Gene. 204 (1–2): 35–46. doi:10.1016/s0378-1119(97)00509-x. PMID9434163.
Haridas V, Shrivastava A, Su J, Yu GL, Ni J, Liu D, Chen SF, Ni Y, Ruben SM, Gentz R, Aggarwal BB (Nov 1999). "VEGI, a new member of the TNF family activates nuclear factor-kappa B and c-Jun N-terminal kinase and modulates cell growth". Oncogene. 18 (47): 6496–504. doi:10.1038/sj.onc.1203059. PMID10597252. S2CID7013492.
Prehn JL, Mehdizadeh S, Landers CJ, Luo X, Cha SC, Wei P, Targan SR (Jul 2004). "Potential role for TL1A, the new TNF-family member and potent costimulator of IFN-gamma, in mucosal inflammation". Clinical Immunology. 112 (1): 66–77. doi:10.1016/j.clim.2004.02.007. PMID15207783.
Kang YJ, Kim WJ, Bae HU, Kim DI, Park YB, Park JE, Kwon BS, Lee WH (Mar 2005). "Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis". Cytokine. 29 (5): 229–35. doi:10.1016/j.cyto.2004.12.001. PMID15760679.
Jin T, Guo F, Kim S, Howard A, Zhang YZ (Dec 2007). "X-ray crystal structure of TNF ligand family member TL1A at 2.1A". Biochemical and Biophysical Research Communications. 364 (1): 1–6. doi:10.1016/j.bbrc.2007.09.097. PMID17935696.
