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Microglia-Mediated Prevention of Traumatic Neurodegeneration
Published in Martin Berry, Ann Logan, CNS Injuries: Cellular Responses and Pharmacological Strategies, 2019
Solon Thanos, Rita Naskar, Peter Heiduschka
Microglia in the adult retina may also participate in synaptic remodelling, based on the fact that they accumulate in both PL, where retinal neurons make synaptic contacts, but are excluded from nuclear layers devoid of synapses. Murabe and Sano43 showed that microglial processes often encircle synapses in the rat cerebral cortex, where they may be involved in the release of neurotransmitters.22,43 Ramified microglia could act as highly efficient clearing systems in neuronal-rich regions. Microglia could favour axonal growth by producing thrombospondin during development, as this extracellular matrix protein promotes neurite outgrowth in cultured neuronal cells. The expression of thrombospondin in relation to the distribution of microglia has been investigated in the developing rat brain using immunocytochemistry.44 A cell population displaying the morphology and distribution of brain macrophages is labelled during early postnatal life, as are ramified microglia. Little is known about a potential role for microglia in neuronal and glial support. Elkabes et al.45 showed that microglia express neurotrophins in a region-specific manner and that within any region only subpopulations elaborate trophins. Immunohistochemical studies on normal human retinas46 indicate that similar populations of microglia are immunoreactive to CD45, MHC I, and MHC II, while relatively few microglia (about 10%) are immunoreactive for human macrophage (S22) antigens, supporting the view of microglial heterogeneity.
Angiogenesis
Published in John H. Barker, Gary L. Anderson, Michael D. Menger, Clinically Applied Microcirculation Research, 2019
Thrombospondin (160 kDa, glycoprotein) is found in platelet α-granules. It is homologous to Gp 140 (140 kDa, glycoprotein), which is promoted by an active cancer suppressor gene. Both inhibit migration of endothelial cells and neovascularization.50 Another factor found in platelet α-granules, which is anti-angiogenic, is platelet factor IV (28 kDa).51 This protein is able to block growth factor-dependent endothelial cell stimulation. This effect can be blocked by readdition of growth factor. Perhaps in this case there exists a balance of platelet proteins which control angiogenesis, since they also contain an angiogenic factor (PD-ECGF).50
Fibrinolytic System
Published in Hau C. Kwaan, Meyer M. Samama, Clinical Thrombosis, 2019
Hau C. Kwaan, M. M. Samama, G. Nguyen
There are other modulators of fibrinolysis, including histidine-rich glycoproteins which form a reversible complex with plasminogen and are estimated to bind approximately 50% of the circulating plasminogen.56 Thrombospondin, a glycoprotein found in the α granules of platelets, also binds plasminogen and may form a ternary complex with fibrin and t-PA. It is believed to enhance the extravascular plasminogen activation by t-PA.57
Elevated Levels of Endoglin, Endostatin, FGF-α, HGF, and Thrombospondin-2 in Aqueous Humor of nAMD Patients
Published in Ocular Immunology and Inflammation, 2022
Zhiqing Chen, Kailin Chen, Jinyu Li, Junhui Shen, Wen Xu
In this study, we showed that the anti-angiogenic factors endostatin and thrombospondin-2 were highly upregulated in the nAMD group. The pro-angiogenic environment in nAMD facilitates the overexpression of anti-angiogenic factors could be one of the reasons. Tatar et al.29 and Muether et al.21 have reported the aqueous concentrations of endostatin in nAMD patients, and both of them reported similar results of elevated endostatin in nAMD patients. Thrombospondin-2 are mainly expressed by pericytes in retinal vasculature, which is further enhanced under oxidative stress.30,31 Thrombospondin-2 and thrombospondin-1 are from one subfamily, and both contain type 1 repeat domains that confer their antiangiogenic activity.32 Thrombospondin also plays a vital role in the immune privilege of the eye.33 Muether et al.21 claimed that thrombospondin-2 levels decreased in patients with nAMD compared with that in controls, which was contrary to our results. In addition, our study showed that thrombospondin-2 levels were positively correlated with GLD and MRT-3 mm at baseline. One possibility could be the small sample sizes for both studies that resulted in relatively large variants, and another possibility could be the patients with different stages or subtypes of nAMD were enrolled.
Advances in the clinical use of collagen as biomarker of liver fibrosis
Published in Expert Review of Molecular Diagnostics, 2020
Steffen K. Meurer, Morten A. Karsdal, Ralf Weiskirchen
Collagens have a long range of binding proteins, including components of the wound healing cascade [102] such as von-Willebrand-factor, and ranges of fibronectin, thrombospondin motifs that have been shown to interact with an array of proteins [97]. Collagens require a diverse set of chaperones which are essential for proper folding of the collagen and which are essential for obtaining the rigid 3-dimensional structure. These proteins include (i) Cartilage oligomeric protein (COMP), which is binding 5 individual α chains making sure that they are folded properly, (ii) heat shock protein 47 (HSP47), which binds type I collagen and other fibrillar collagens, with up to 20 molecules per protein, to ensure correct processing in the endoplasmic reticulum, (iii) Periostin and SPARC, which bind collagens albeit their exact role remains to be fully understood, and (iv) the very important enzymes ADAMTS-2 and BMP-1, which process the pro-peptides of collagens allowing them to form the tight fibrils in the collagen fibers. The location of these molecules is visualized in Figure 6.
The role of extracellular matrix components in angiogenesis and fibrosis: Possible implication for Systemic Sclerosis
Published in Modern Rheumatology, 2018
Vasiliki Liakouli, Paola Cipriani, Paola Di Benedetto, Piero Ruscitti, Francesco Carubbi, Onorina Berardicurti, Noemi Panzera, Roberto Giacomelli
Thrombospondins (TSPs) are a family of extracellular glycoproteins, including five members (TSP-1 to TSP-5) displaying well known anti-angiogenic properties [24]. The TSPs appear to function at the cell surface, bringing together membrane proteins, growth factors, cytokines, and extracellular proteases that regulate ECM structure and cellular phenotype. Loss of TSP-1 or TSP-2 during embryogenesis is not lethal but resulting in increased vascular density [25,26]. In contrast, transgenic mice with targeted overexpression of TSP-1 exhibit a decreased vascular density [27]. TSP-1 is largely released by hypoxic ECs, and hypoxia-conditioned media from these ECs blocks proliferation and induces apoptosis in microvascular endothelial cells (MVECs), an effect that is reduced when TSP-1 is blocked. Interestingly, recombinant TSP-1 blocks proliferation and induces apoptosis of ECs at the same concentration found in SSc plasma and this, is an effect that occurs in the presence of elevated VEGF levels [28]. It has been supposed that this anti-angiogenic mechanism of TSP-1, is mediated by the binding of TSP-1 to its trans-membrane glycoprotein receptor CD36 as well as the β1 integrin that are associated with the VEGF receptor-2 (VEGFR-2) [29]. The binding of TSP-1 to CD36 results in the suppression of angiogenesis by inhibiting EC migration and inducing EC apoptosis [30]. Additionally to the anti-angiogenic role, the overexpressed TSP-1 activates latent TGF-β by its RFK motif and contributes to accumulation of ECM [31].