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THBS1 activates CD47. 68 / 73
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"CD47 has been shown to associate with caveolin-1, a negative regulator of eNOS, in lung endothelial cells; upon activation of CD47 by TSP1, this association is disrupted leading to a decrease in caveolin-1 and increase in eNOS superoxide production[ xref ]."
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"While TSP1 is known to modulate distinct T cell functions by engaging alpha4beta1 and CD47 in T cells, this is the first report to implicate VEGFR2 in the ability of TSP1 to modulate anti-CD3-mediated T-cell activation."
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"CD47 Independent Effects Mediated by the TSP Derived 4N1K Peptide."
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"In addition to the effects of TSPs on physiological angiogenesis, recent evidence suggests that TSP-1 is able to modulate nitric oxide (NO) controlled blood pressure via its receptor CD47 and integrin associated protein (CD47 and IAP)."
19798592
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"TSP1 mediated activation of the CD47 receptors antagonizes nitric oxide signaling via endothelial cell derived nitric oxide synthase (eNOS) 15, which is important in cell migration and proliferation 16."
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"Moreover, TSP1 was found to inhibit VEGFR2 signaling by disrupting the association of CD47 with VEGFR2 [XREF_BIBR], suggesting that CD47 is involved in TSP1 mediated inhibition of angiogenesis."
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"We recently demonstrated that the two main genetic AMD-risk variants, CFH Y402H and a haplotype of 10q26, curb TSP-1 activation of CD47 that is necessary for homeostatic MP elimination and the resolution of acute inflammation in the subretinal space [ xref , xref ]."
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"CD47 stimulation by mAb or a thrombospondin-1 peptide induced naive or memory CD4+ CD25- T cells to become suppressive."
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"Thrombospondin-1 (TSP-1), a protein released by platelets, can activate CD47, which leads to NO production and inhibition of signal transduction."
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"Others have reported that the activation of CD47 by the endogenous ligand TSP-1 or the peptide 4N1K triggers complex cell death pathways in a wide range of cell types such as T cells, leukemia cells, monocytes, and breast tumor cells ( xref ; xref , xref ; xref ; xref )."
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"Thrombospondin-1 triggering of its cell membrane receptor CD47 induces some human T cell apoptosis on its own [XREF_BIBR, XREF_BIBR]."
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"Activation of CD47, either by TSP1 or the CD47-specific TSP1-derived peptide 7N3, has been shown to increase the production of ROS in cells."
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"Finally, treating wild type animals with a CD47 monoclonal antibody, that inhibits TSP1 activation of CD47, enhanced SkBF in both young and aged animals."
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"Also, as we have reported that CD47 controls basal 12 and ischemic blood flow, XREF_BIBR - XREF_BIBR and ischemia is known to occur in LVHF, 63 it is interesting to hypothesize that TSP1 mediated activation of CD47 may also limit cardiac blood flow under these conditions."
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"The studies also suggest CD47 activation by a TSP1 specific peptide may play a central role."
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"In summary, CD47 activation by TSP-1 may regulate the endothelial and astrocytic production of VEGF and MMP-9, which are two of the major mediators involved in neurovascular injury and barrier leakage after cerebral ischemia."
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"CD47 Activation by Thrombospondin-1 in Lymphatic Endothelial Cells Suppresses Lymphangiogenesis and Promotes Atherosclerosis ."
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"However, since TSP triggering of CD47 also increases T cell Fas sensitivity, we investigated whether T cell triggering by the combination of TRAIL and CD47 might increase control T cell apoptosis sensitivity to TRAIL similarly to what occurs with trauma patients ' T cells [XREF_BIBR]."
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"The observed changes in MV stability induced by TSP-1 activation of CD47 after contusion may only negligibly affect recovery from SCI, as TSP-1 −/− mice are not significantly different in functional recovery from WT mice."
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"While this provides an exciting area for future research, numerous studies of CD47 signaling functions that have been published so far focused on CD47 activation by TSP-1."
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"Herein then we tested the hypothesis that temperature- and age-associated changes in sKBF are limited by TSP1-activation of the cell receptor CD47."
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"13 TSP1 mediated activation of the CD47 receptors antagonizes nitric oxide signaling via endothelial cell derived nitric oxide synthase, 15 which is important in cell migration and proliferation."
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"TSP-1 mediated CD47 triggering can increase TRAIL mediated primary stimulated T cell apoptosis by diminishing several of these T cell activation pathways."
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"Antibody blockade of TSP1 or morpholino suppression of CD47 dramatically enhanced survival of random tissue flaps."
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"In vivo, CD47 activation by TSP-1 might enhance acute EC cytotoxicity or apoptosis after injury in addition or as opposed to negatively regulating proliferation."
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"As an example, TSP1 may activate endothelial receptors CD36 or CD47 differentially or they can induce different responses depending on the type of integrin expressed; for instance, TSP1 inhibits endothelial migration in the microvasculature via binding with CD36 ( xref , xref ), but it could also enhance chemotaxis by binding to integrins α3β1and α6β1in HDMEV ( xref )."
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"The observed changes in MV stability induced by TSP-1 activation of CD47 after contusion may only negligibly affect recovery from SCI, as TSP-1 -/- mice are not significantly different in functional recovery from WT mice."
21168495
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"Activation of CD47 by TSP1 induces Nox1-mediated ROS production via PLC, xref further supporting regulation of ROS signaling by matricellular proteins."
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"We recently demonstrated that TSP-1 activation of CD47 sensitizes infiltrating subretinal MPs to RPE induced death and elimination [ xref , xref ]."
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"Thus, although preclinical cancer studies generally interpret B6H12 inhibition as evidence for SIRPalpha mediated functions of CD47 in vitro and in xenograft models, such inhibition may result from SIRPalpha independent mechanisms including perturbing TSP1- or integrin mediated activities of CD47."
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"This effect of TSP1 and 4N1K on alpha2beta1 mediated chemotaxis requires IAP."
10525543
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"In addition to binding directly to αvβ3 integrin, TSP-1 can activate αvβ3 integrin signalling by binding to a co-receptor called integrin-associated protein."
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"Membrane bound TSP-1 in APCs can also help activate TGF-beta in the vicinity of responding T cells engaged during antigen presentation and by ligating CD47 on APCs, it inhibits expression of Th1 promoting inflammatory cytokine XREF_BIBR, XREF_BIBR."
24559320
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"CD47 Activation by Thrombospondin-1 in Lymphatic Endothelial Cells Suppresses Lymphangiogenesis and Promotes Atherosclerosis."
37259865
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"In addition to the effects of TSPs on physiological angiogenesis, recent evidence suggests that TSP-1 is able to modulate nitric oxide (NO) controlled blood pressure via its receptor CD47 and integrin associated protein (CD47 and IAP)."
19798592
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"TSP-1 activation of CD47 induces apoptosis via caspase-dependent and independent mechanisms in cultured cerebral cortical neurons and NB4 cells, respectively ( xref ; xref )."
21168495
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"Herein then we tested the hypothesis that temperature- and age associated changes in sKBF are limited by TSP1 activation of the cell receptor CD47."
23275312
sparser
"In summary, CD47 activation by TSP-1 may regulate the endothelial and astrocytic production of VEGF and MMP-9, which are two of the major mediators involved in neurovascular injury and barrier leakage after cerebral ischemia."
20364320
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"CD47 stimulation by mAb or a TSP1 peptide induced naive or memory CD4+ CD25- T cells to become suppressive."
20300551
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"TSP-1 triggering of CD47 is known to increase activated human T cells ' susceptibility to Fas mediated apoptosis [XREF_BIBR]."
22926077
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"A previous study showed that TSP1 inhibits VEGFR2 signaling by disrupting the association of CD47 with VEGFR2 [XREF_BIBR]."
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"These data indicate that TSP‐1 contributes to both the formation of CD47 aggregates on RBCs and the clearance of aging RBCs.2.6 Role of lipid rafts in 4N1K-induced CD47 rearrangement on RBCs from aged mouse."
32866348
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"12 Previous studies have shown that the antiangiogenic activity of TSP1 is mediated by its receptors CD36 XREF_BIBR, XREF_BIBR and CD47."
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"These studies suggest that the expression pattern of CD47 on RBCs might be important in determining its TSP‐1 binding capacity and that TSP‐1/CD47 interaction may promote phagocytosis by affecting CD47‐SIRPα signaling or providing pro‐phagocytic signals."
32866348
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"Next, we investigated whether CD47 activation by TSP1 limits tissue blood flow in vivo following IR."
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"Whereas the CD47 interaction with SIRPalpha on macrophages modulates phagocytosis, ligation of thrombospondin-1 or anti-CD47 antibodies with CD47 on Tcells triggers CD47 intracellular signaling and anti-inflammatory effects, and it results in reduced proliferation or even Tcell death."
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"The results from this study demonstrate that glucose regulation of TSP-1, by reducing its lysosomal degradation, enhances IGF-I signaling in SMC by protecting CD47 and IAP from cleavage thereby increasing its association with its ligands SHPS-1 and alphaVbeta3."
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"Increased TSP1 within the ECM could lead to increased CD47 activation thereby contributing to alphavbeta3-integrin-mediated CLAN formation in DEX treated HTM cells."
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"In hypoxic environments and in PH, TSP-1- induced CD47 activation led to decreased caveolin-1 (eNOS binding protein) expression, subsequent uncoupling of endothelial nitric oxide synthase (eNOS) and ROS production."
23372933
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"CD47 Activation by Thrombospondin-1 in Lymphatic Endothelial Cells Suppresses Lymphangiogenesis and Promotes Atherosclerosis."
37259865
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"TSP-1 is increased post-injury and can trigger CD47 (its receptor) on T cells to induce apoptosis [XREF_BIBR, XREF_BIBR]."
22926077
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"Conversely, in hypoxic animals and cell cultures activation of CD47 by TSP1 disrupts this constitutive interaction, promoting eNOS-dependent superoxide production, oxidative stress, and PAH."
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"TSP-1 activation of CD47 induces apoptosis via caspase dependent and independent mechanisms in cultured cerebral cortical neurons and NB4 cells, respectively."
21168495
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"Conversely, in hypoxic animals and cell cultures activation of CD47 by TSP1 disrupts this constitutive interaction, promoting eNOS-dependent superoxide production, oxidative stress, and PAH."
22215724
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"Thrombospondin-1 can promote leukocyte adhesion directly by engaging cell surface integrins and indirectly by engaging its receptor CD47 8."
26139855
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"TSP1 induced CD47 receptor activation 41 inhibits the NO signaling pathway."
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"TSP-1 stimulation of CD47 (a member of immunoglobulin superfamily, component of the beta3 integrin complex, expressed on T cells and polymorphonuclear cells, having a role in maintaining immune tolerance) induces the inhibition of releasing IL-2 [XREF_BIBR, XREF_BIBR]."
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"Activated platelets can release soluble TSP-1, which goes on to trigger even more CD47 pathways."
19360900
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"In human monocytes and murine macrophages TSP1 enhances PMA mediated O2 - production, likely via a CD47 independent manner since recombinant TSP1 derived domains of the N- but not the CD47 interacting C-terminus replicated the effects of the whole protein [XREF_BIBR]."
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"Intact TSP1 at physiological 10-100 pM concentrations XREF_BIBR XREF_BIBR is sufficient to induce CD47 signaling, but insufficient to signal through CD36, which requires greater than 1nM TSP1 XREF_BIBR."
26813769
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"Finally, treating wild type animals with a CD47 monoclonal antibody, that inhibits TSP1 activation of CD47, enhanced SkBF in both young and aged animals."
23275312
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"The deficit in aged MuSC function in regeneration can be overcome either by morpholino-mediated blockade of CD47 alternative polyadenylation or antibody blockade of thrombospondin-1/CD47 signaling, leading to improved regeneration in aged mice, with therapeutic implications."
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"Our data further suggest that TSP-1 triggering of CD47 induction of SHP-1 activation can critically contribute to TRAIL triggered post injury apoptosis by depressing NFkappaB."
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"Activation of CD47 by TSP-1 ultimately inhibits Ca 2+ /calmodulin-mediated activation of eNOS ( xref ), activation of soluble guanylate cyclase (sGC) by nitric oxide (NO; xref ), and downstream activation of cGMP-dependent protein kinase ( xref )."
33869231
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"Our data showed that there was a significant induction of CD47 protein but not TSP-1 expression after cold ischemia (XREF_FIG)."
25482981
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"The results from this study demonstrate that glucose regulation of TSP-1, by reducing its lysosomal degradation, enhances IGF-I signaling in SMC by protecting CD47 and IAP from cleavage thereby increasing its association with its ligands SHPS-1 and alphaVbeta3."
20689700
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"The post-injury T cell anergy developing subsequent to TSP-1 triggering of CD47 could also result from other CD47 triggered inhibitory functions [XREF_BIBR]."
22926077
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"Integrin-associated matricellular protein receptors such as CD47 and CD36 have recently been shown to be involved in pathological ROS production. xref Activation of CD47 and CD36 by thrombospondin-1 (TSP1) inhibits NO signaling xref in VSMCs and may contribute to eNOS uncoupling. xref Additionally, knockout studies of CD36 have implicated CD36 activity in the regulation of Nrf2 nuclear export and degradation, xref which ultimately results in higher levels of oxidative stress due to reduced antioxidant expression."
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