Thrombospondins

Thrombospondins are a family of secreted matricellular glycoproteins that regulate cell–matrix interactions. In humans, the family comprises THBS1 through THBS5. Thrombospondin-1 and thrombospondin-2 form homotrimers, while thrombospondin-5 (also known as cartilage oligomeric matrix protein or COMP) forms pentamers; thrombospondin-3 and thrombospondin-4 are also secreted multimers. They share modular domains that mediate protein–protein interactions, including thrombospondin type 1 repeats and a C-terminal domain. They bind a range of matrix components and cell-surface receptors such as integrins, CD36, CD47, and heparan sulfate proteoglycans, enabling diverse signaling outcomes.

Functions of thrombospondins include modulation of cell adhesion, migration, proliferation, and extracellular matrix remodeling. They influence angiogenesis, usually inhibiting it via CD36-dependent pathways (notably TSP-1 and TSP-2), though context-dependent effects exist. They can activate latent transforming growth factor-beta by promoting release from the latency-associated peptide. They participate in wound healing, immune regulation, and neural development, including synaptogenesis in the central nervous system.

Distribution and roles in disease: thrombospondins are found in platelets and connective tissues, released during injury and inflammation. As matricellular proteins, they act transiently to tune signaling rather than provide structural extracellular matrix. Dysregulation of thrombospondins is linked to cancer, fibrosis, cardiovascular disease, and ocular disorders, making them topics of ongoing research and potential therapeutic targets or biomarkers.