Thrombospondin-1 (human):Fc (human) (rec.)

Thrombospondin-1 (TSP1) is a 150-180kDa calcium-sensitive protein that is secreted as a disulfide-linked homotrimer. Within the thrombospondin family, TSP-2 is also homotrimeric, while TSP-3, -4, and -5/COMP are homopentameric. TSP-1 regulates a wide range of cellular functions including their interactions with other cells and with the extracellular matrix (ECM). TSP-1 contains an N-terminal laminin G-like globular domain, an extended central region with one VWFC domain, 3 TSP type-1 domains, 2 EGF-like domains, and 8 TSP type-3 domains and a globular TSP C-terminal domain. Distinct regions of TSP-1 have been associated with binding to particular ECM or cellular molecules. TSP-1 counteracts the angiogenic, hypotensive and anti-thrombotic effects of nitric oxide (NO). It binds and neutralizes VEGF, blocks VEGFR-2 signaling on vascular endothelial cells (EC) and destabilizes adhesive contacts between EC. TSP-1’s actions on vascular smooth muscle cells support arterial tone and blood pressure in the presence of vasodilatory stimulation. It is released from activated platelets and enhances platelet aggregation and adhesion. TSP-1 also plays an important role in wound repair and tissue fibrosis by binding latent TGF-β and inducing release of the active cytokine from the latency associated peptide (LAP). TSP-1 dampens adaptive immune responses by inducing the differentiation of regulatory T cells and inhibiting TCR signaling. In the nervous system, it promotes excitatory synapse formation and supports the integration of neural progenitor cells into the olfactory bulb. In addition, TSP-1 is released by apoptotic cells and promotes macrophage-mediated debris clearance.