The Thrombospondins

Abstract

Thrombospondins are evolutionarily conserved, calcium-binding glycoproteins that undergo transient or longer-term interactions with other extracellular matrix components. They share properties with other matrix molecules, cytokines, adaptor proteins, and chaperones, modulate the organization of collagen fibrils, and bind and localize an array of growth factors or proteases. At cell surfaces, interactions with an array of receptors activate celldependent signaling and phenotypic outcomes. Through these dynamic, pleiotropic, and context-dependent pathways, mammalian thrombospondins contribute to wound healing and angiogenesis, vessel wall biology, connective tissue organization, and synaptogenesis. We overview the domain organization and structure of thrombospondins, key features of their evolution, and their cell biology. We discuss their roles in vivo, associations with human disease, and ongoing translational applications. In many respects, we are only beginning to appreciate the important roles of these proteins in physiology and pathology.T hrombospondins (TSPs) comprise a conserved family of extracellular, oligomeric, multidomain, calcium-binding glycoproteins. In general, basal metazoa and protostomes encode a single TSP in their genomes and deuterostomes have multiple TSP genes. The TSPs of mammals have many complex tissue-specific roles, including activities in wound healing and angiogenesis, vessel wall biology, connective tissue organization, and synaptogenesis. These activities derive mechanistically from interactions with cell surfaces, growth factors, cytokines, or components of the extracellular matrix (ECM) that collectively regulate many aspects of cell phenotype. Emerging evidence on the functions of TSPs in invertebrates suggests that ancient functions include bridging activities in cell-cell and cell-ECM interactions. Knowledge of TSP domain structures provides a rational basis for understanding their roles in vivo and associations with human disease and is assisting ongoing translational applications. DOMAIN ARCHITECTURE AND DOMAIN STRUCTURESThe domain architectures of representative TSP polypeptides are shown in Figure 1A. The invariant carboxy-terminal regions comprise a series of EGF-like domains, thirteen calcium-binding type 3 repeats, and a carboxy-terminal domain structurally homologous to the L-type lectin

Normal ranges of angiogenesis regulatory proteins in human platelets

“…We also report VEGF levels in platelets of normal individuals to be 0.74 ± 0.37 pg/10 6 platelets (range 0.15-1.86), values very similar to those reported by Salven et al [27] [0.5 pg/10 6 platelets (range 0.1-1.6)]. The levels of TSP-1 in plasma have been described as 180 ng/mL [28], which was lower than those determined in our studies (559 ± 272 ng/mL). We found no direct measurements of TSP-1 in platelets in the literature.…”

Escherichia coli K1 Promotes the Ligation of CD47 with Thrombospondin-1 To Prevent the Maturation of Dendritic Cells in the Pathogenesis of Neonatal Meningitis

“…Its expression is highly regulated by different hormones and cytokines, and is developmentally controlled (16). The levels of TSPs in body fluids and their distribution in tissues have been correlated with various pathological states (17). TSP-1 is transiently expressed at high concentrations in damaged and inflamed tissues.…”

Inducible genetic system for the axolotl

“…Previously, we had found that two genes encoding axolotl thrombospondins, thrombospondin-1 (tsp-1) and thrombospondin-4 (tsp-4), displayed dynamic expression patterns in discrete cell types during the course of limb regeneration (32). Although thrombospondins have been implicated in numerous aspects of mammalian biology (33), including some that may be pertinent to regeneration such as wound healing and angiogenesis, nothing is known about their potential role in appendage regeneration.…”