Disease relevance of THBS1

• Because thrombospondin is a cell-substrate adhesion molecule, its role in the loss of cellularity that occurs in the trabecular meshwork of the aging eye and in eyes with primary open-angle glaucoma is worthy of further investigation [1].
• Thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein, inhibits neovascularization and is implicated in the regression of tumor growth and metastasis [2].

High impact information on THBS1

• In contrast, exposure of SMCs to vitronectin (1.0 micrograms/cm2) or thrombospondin (0.25 micrograms/cm2), two known ligands for alphaVbeta3, resulted in enhancement of the IGF-I-stimulated IRS-1 response [3].
• Interaction of thrombospondin-1 and heparan sulfate from endothelial cells. Structural requirements of heparan sulfate [4].
• Cell surface-associated heparan sulfate proteoglycans, predominantly perlecan, are involved in the process of binding and endocytosis of thrombospondin-1 (TSP-1) by vascular endothelial cells [4].
• Further depolymerization of the binding oligosaccharides revealed that the glucosamine residues within the TSP-1-binding sequences are not continuously N-sulfated [4].
• The present findings implicate specific structural properties for the HS domain involved in TSP-1 binding and indicate that they are distinct from the binding sequence described for basic fibroblast growth factor, another HS ligand and a potential antagonist of TSP-1 [4].

Biological context of THBS1

• In the presence of thrombospondin-1 cells did not organize in follicle-like structures but, in contrast, spreaded and reached confluency independently of cell proliferation [5].
• The addition of 1.0 microg/ml of this mutant did not inhibit the protein synthesis or cell migration responses to IGF-I plus TS-1 [6].
• Our data suggest that the control of thyroid follicle formation may operate at least in part through regulation of the production of the matricellular protein TSP1, which acts as a negative modulator of the cell-cell adhesion process involved in thyroid follicle morphogenesis [7].
• Thrombospondin and osteopontin bind to insulin-like growth factor (IGF)-binding protein-5 leading to an alteration in IGF-I-stimulated cell growth [8].
• Given that there are three binding sites per molecule and that thrombospondin appears to form polymeric aggregates with itself, significant binding energies could be developed [9].

Anatomical context of THBS1

• Polarized secretion of thrombospondin is opposite to thyroglobulin in thyroid epithelial cells [10].
• Gel filtration of secreted thrombospondin eluted at a high molecular weight, suggesting complexation with components of the extracellular matrix [10].
• Immunoprecipitation of thrombospondin from media bathing primary thyrocytes and the FRTL5 cell line quantitatively recovered p500, confirming its identity and indicating an epithelial origin [10].
• This suggested that the presence of thrombospondin in the trabecular meshwork was probably due to local synthesis [1].
• These results, together with the stimulating effect of TPA on TSH mediated cell proliferation, argue for a role of thrombospondin in cell adhesion and migration events within the thyroid epithelium [11].

Associations of THBS1 with chemical compounds

• The adhesive properties of thrombospondin-1 for thyroid cells were shown to be mediated by both the amino-terminal heparin-binding domain and the RGD domain of thrombospondin-1 [5].
• TGF-beta1 strongly activated the production of thrombospondin-1 and (alpha)vbeta3 integrin in a concentration-dependent manner whereas the expression of thyroglobulin was unaffected [5].
• Treatment of the insoluble matrix with beta-mercaptoethanol led to an enriched extraction of the approximately 160-kD form of thrombospondin [1].
• No inhibition was observed in the presence of putative LPA receptor antagonists suramin or thrombospondin [12].
• Colloidal gold conjugation of thrombospondin fragments proved to be useful for cytochemical characterization of molecular domains [13].

Physical interactions of THBS1

• Integrin-associated protein binding domain of thrombospondin-1 enhances insulin-like growth factor-I receptor signaling in vascular smooth muscle cells [14].

Other interactions of THBS1

• Thrombospondin-1 reproduced the effect of TGF-beta1 [5].
• Down-regulated expression of A disintegrin and metalloproteinase with thrombospondin-like repeats-1 by progesterone receptor antagonist is associated with impaired expansion of porcine cumulus-oocyte complexes [15].
• Immunoprecipitation and quantitation revealed that the incorporation of [35S]methionine into fibronectin is reduced whereas thrombospondin synthesis was increased [16].
• In supershift assay, potential regulatory elements in this region, SP1 and GATA-1, were not responsive to the inhibition of TSP-1 expression by PMA [2].
• Compared with the normal artery, the level of alpha-smooth muscle actin mRNA decreased, and there was a concomitant increase in vimentin, fibronectin and thrombospondin mRNA levels [17].

Analytical, diagnostic and therapeutic context of THBS1

• Affinity chromatography on immobilized TSP-1 demonstrated that nearly all intact HS chains possessed binding affinity, whereas after heparinase III treatment only a small proportion of oligosaccharides were bound with similar affinity to the column [4].
• Further, immunofluorescence showed cellular codistribution of thrombospondin and thyroglobulin, although thrombospondin exhibited predominantly an extracellular, basolateral deposition [10].
• By using western blotting with a monoclonal antibody against the calcium-binding domain of thrombospondin, the authors detected a 180-kD glycated polypeptide in the trabecular meshwork tissue of normal human and porcine eyes [1].
• We used antisera directed against human platelet thrombospondin (TSP) and microfibril-associated GP 128 to localize the presence of these glycoproteins in fixed sections of human placenta or porcine arteries and skin by immunogold labeling, using electron microscopy [18].

References