Tumor necrosis factor ligand superfamily member 12 also known as TNF-related weak inducer of apoptosis (TWEAK) is a protein that in humans is encoded by the TNFSF12 gene.[5][6][7]
TWEAK was discovered in 1997.[5] The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This protein is a ligand for the FN14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. Leukocytes are the main source of TWEAK including human resting and activated monocytes, dendritic cells and natural killer cells.[8] TWEAK can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis.[7]
Excessive activation of the TWEAK pathway in chronic injury has been described to promote pathological tissue changes including chronic inflammation, fibrosis and angiogenesis.[9] In chronic liver disease, for example, TWEAK expression is enhanced and causes hepatic stellate cells, which are key regulators of liver fibrosis, to proliferate.[10]