Tissue factor.
Tissue factor is the primary cellular initiator of blood coagulation via interaction with coagulation factor VII. Aberrant expression of tissue factor is responsible for thrombosis during septic shock, atherosclerosis and cancer. However, recent evidence has accumulated that tissue factor may have functions beyond controlling fibrin-dependent hemostasis. It is expressed as an immediate early gene by growth factors and cytokines, it transduces intracellular signals via its cytosolic domain, triggers production of growth factors and has been implicated in immune function, smooth muscle migration and metastasis, the latter via mechanisms requiring intracellular signaling as well as the proteolytic activity of the tissue factor-factor VIIa complex. Further evidence for a possible alternative role of tissue factor has been provided from tissue factor gene inactivation studies, indicating that tissue factor controls vascular integrity by affecting the maturation of the muscular wall around endothelial cell lined channels. Surprisingly, however, deficiency of factor VII does not affect vascular integrity and tissue factor may act independently of fibrin formation during embryogenesis. Elucidation of the mechanism of its action may provide insights for selective interference with the hemostatic versus morphogenic properties of tissue factor.
Carmeliet
P
P
Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, Leuven, Belgium. peter.carmeliet@med.kuleuven.ac.be
Collen
D
D
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D011487:Protein Conformation; D013925:Thromboplastin / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D013925:Thromboplastin