Thrombospondin1

Thrombospondin-1 (TSP-1) is a secreted extracellular glycoprotein of the thrombospondin family, encoded by the THBS1 gene in humans. It forms homotrimers and is produced by a variety of cell types, including platelets, endothelial cells, fibroblasts, and smooth muscle cells. As a matricellular protein, TSP-1 modulates cell signaling at the interface between cells and the extracellular matrix rather than serving primarily as a structural component.

TSP-1 interacts with a range of partners, including the receptors CD36 and CD47, integrins, and components of the extracellular matrix such as heparan sulfate proteoglycans, collagen, and fibronectin. Through these interactions it influences cell adhesion, migration, proliferation, and inflammatory responses. A key feature of its activity is anti-angiogenic effect: TSP-1 inhibits endothelial cell proliferation and migration and can promote endothelial cell apoptosis, in part via CD36 signaling.

In addition to its anti-angiogenic actions, TSP-1 can activate latent transforming growth factor-beta (TGF-β), contributing to fibrotic and immune regulatory processes in a context-dependent manner. It also participates in wound healing and tissue remodeling and can modulate nitric oxide signaling through CD47, linking vascular function to platelet activity.

Biologically, TSP-1 influences angiogenesis, thrombosis, fibrosis, and cancer progression. Levels and activity of thrombospondin-1 are studied in various diseases, and therapeutic approaches have explored TSP-1–derived peptides and strategies to modulate its pathways. The protein’s effects are complex and highly context dependent, reflecting its role as a regulatory mediator in intercellular and matrix signaling networks.