Thrombospondins

The active portion of TGF-P (the C-terminal region) is composed of a cysteine knot, nine conserved cysteine residues, of which eight form disulfide bonds within the molecule 

Many cells secrete at least one of the three immature forms of TGF-P, and essentially all cells have receptors that respond to the presence of mature TGF-P in the stroma. In the periodontium, TGF-P stimulates fibroblast and osteoblast proliferation during connective tissue or bone remodeling (Sect. 10.1.3), and maintains the proliferation of dentally attached epithelial cells (Sect. 5.2.3). The linker domains that connect calcium binding domains in fibrillin are identical to the sequence of protein receptors that bind to TGF-P (Sect. 6.1.1). 

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Thrombospondins Inhibits EC proliferation, migration and induces EC apoptosis by binding to endothelial CD36... 

The growing list of endogenous inhibitors of angiogenesis holds great promise for therapeutic applications (Table 2). Substances most advanced in clinical development include Endostatin, Angiostatin, Interleukin-12, Thrombospondin, and Tumstatin. As... 

Sage E Regulation of interactions between cells and extracellular matrix a command performance on several stages. J Clin Invest 2001 107 781. (This article introduces a series of six articles on cell-matrix interaction. The topics covered are cell adhesion and de-adhesion, thrombospondins, syndecans, SPARC, osteopontin, and Ehlers-Danlos syndrome. All of the articles can be accessed at www.jci.org.)... 

CD35 C3b receptor CD36 Known to be z macrophage thrombospondin receptor CD40 Present on B cells and follicular dendritic cells CD41 Known to be z platelet glycoprotein... 

Urquidi, V., Sloan, D., Kawai, K., Agarwal, D., Woodman, A. C., Tarin, D., Goodison, S. (2002). Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis. Clin. Cancer Res. 8(1), 61-74. 

The N-terminal sequence of one peptide from the 35 kDa zone of H-gal-GP showed some homology to cathepsin B-like cysteine proteases. Molecular cloning has also identified a thrombospondin homologue associated with the diffusely staining region between zones A and B, a galectin associated with zone D (Newlands et al., 1999) and a low molecular weight (approximately 13 kDa) cysteine protease inhibitor, cystatin. 

Robson, K.J., Hall, J.R., Jennings, M.W., Harris, T.J., Marsh, K., Newbold, C.I., Tate, V.E. and Weatherall, D.J. (1988) Ahighly conserved amino acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood-stages of the human malaria parasite. Nature 335, 79-82. 

Sickle erythrocytes have increased surface expression of CD36. Microvascular endothelial cells do express CD36. Adhesion between these CD36 molecules of the two cells types can be mediated via the bridging ligand thrombospondin". Indeed plasma thrombospondin levels are increased in SCA patients with pain crisis [15]. 

In the normal healthy IVD, the cells not only produce matrix macromolecules and growth factors, they also produce a myriad of proteases [26, 27]. Included in this list of proteases are the matrix metalloproteinases (MMPs) and aggrecanolytic members of the disintegrin and metalloproteinase with thrombospondin motif family (ADAMTS) as well as their respective inhibitors. It is the maintenance of this critical balance that results in a healthy IVD ECM that is subsequently well adapted for its physiologic and biomechanical function. 

Suchard, S. J., Burton, M. J., Stoehr, S. J. (1992). Thrombospondin receptor expression in human neutrophils coincides with the release of a subpopulation of specific granules. Biochem. J. 284, 513-20. 

Bornstein, P., 2001, Thrombospondins as matrix cellular modulators ofceU function, J. Clin. Invest. 107 929-934. 

Manodori, A.B., Barabino, G.A, Lubin, B.H., and Kuypers, F.A, 2000, Adherence of phosphatidylserine-exposing erythrocytes to endothelial matrix thrombospondin. Blood 95 1293-1300. 

SaviU, J.S., Hogg, N., Ren, Y., and Haselett, C., 1992, Thrombospondin cooperates with CD36 and the vitronectin receptor in macrophage recognition of neutrophils undergoing apoptosis,/. Clin. Invest. 90 1513-1522. 

Sugihara, K., Sugihara, T, Mohandas, N., and Hebbel, R.P., 1992, Thrombospondin mediates adherence of CD36-I- sickle reticulocytes to endothelial cells. Blood 80 2634-2642. 

In other chronic inflammatory diseases elevated levels of angiogenic factors were also found. In patients with psoriasis, skin lesions over-expressed IL-8 while the expression of one of the inhibitors of angiogenesis, thrombospondin-1, was downregulated [39]. 

Other platelet membrane glycoproteins that are involved in adhesion reactions are GPIV and GPVI, which play a role in platelet interactions with and activation by collagen (6, 7). GPIV also functions as a receptor for the platelet alpha granule protein thrombospondin (2, 7, 8). Table 1 summarizes the functions of platelet membrane receptors. 

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