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THBS1 activates CD47. 117 / 122
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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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"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 )."
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"Next, we investigated whether CD47 activation by TSP1 limits tissue blood flow in vivo following IR."
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"CD47 activation by TSP1 can be mimicked by the KRFYVVMWKK ( Martinez-Torres et al., 2015 ) that is derived from the first VVM site of TSP1 and does not contain a HTRA1 cleavage site ( Figure S2 B)."
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"However, activated CD47 induced by TSP1 protein could significantly enhance the pinocytosis of Mφ to increase the foam cells in tissues, as implicated in cardiovascular diseases (58); there was no clear evidence to support that CD47 is involved in the regulation of lysosomal activity of Mφ."
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"TSP-1 can activate CD47 on macrophages, affecting pro-inflammatory IL-1β maturation, a critical process for pathogen-induced and metabolic dysregulation-induced inflammation (134)."
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"CD47 stimulation by mAb or a TSP1 peptide induced naive or memory CD4+ CD25- T cells to become suppressive."
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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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"The efficient activation of CD47 by TSP1 necessitates the presence of both VVM sites of TSP1 ( McDonald et al., 2003 ) but can be mimicked by the TSP1-derived 4N1K peptide (KRFYVVMWKK) ( Martinez-Torr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32814029
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"TSP1 activation of CD47 expressed on subretinal MPs triggers their RPE-induced elimination ( Calippe et al., 2017 ), likely acting as a sensitizing factor to cell death induction by RPE factors such a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32814029
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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."
20364320
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"As a pathogenic factor, complement factor H binding with CD11b inhibits TSP1 activation of CD47, whilst inhibiting CD47-mediated MP removal."
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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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"Thrombospondin-1 (TSP-1), a protein released by platelets, can activate CD47, which leads to NO production and inhibition of signal transduction."
32733941
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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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"32 Interestingly, in human arterial vascular smooth muscle cells, TSP1 activation of CD47 targeted the p47phox subunit of Nox to increase superoxide production."
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"Singla et al. demonstrated that deletion of CD47 attenuates the development of atherosclerosis in hypercholesterolemic mice and further found TSP-1 can mediate activation of CD47 in regulating atherosclerosis development [22]."
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"Previous work by this group had shown that thrombospondin-1 (TSP1) is needed to activate the CD47 receptor on mononuclear phagocytes (MPs) to induce the active process of MP elimination from the immun[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The homeostatic elimination of infiltrating MPs is dependent on TSP1-mediated activation of the CD47 receptor and is inhibited by CFH, in particular the AMD-associated CFH(H402) variant ( Calippe et a[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32814029
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"The efficient activation of CD47 by TSP1 necessitates the presence of both VVM sites of TSP1 ( McDonald et al., 2003 ) but can be mimicked by the TSP1-derived 4N1K peptide (KRFYVVMWKK) ( Martinez-Torr[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
32814029
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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)."
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"CD47 activation by TSP1 can be mimicked by the KRFYVVMWKK ( Martinez-Torres et al., 2015 ) that is derived from the first VVM site of TSP1 and does not contain a HTRA1 cleavage site ( Figure S2 B)."
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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."
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"Thrombospondin-1 (TSP-1) is a protein released by platelets, is proatherogenic ( Rogers, Sharifi-Sanjani, Csányi, Pagano, & Isenberg, 2014 ), and activates CD47, which causes inhibition of NO producti[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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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"Picomolar concentrations of TSP1-activated CD47 [ xref ], suggesting that this interaction dominates under most conditions."
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"Tsp-1 mediates unique downstream effects via its receptors αvβ3, CD36, and CD47 [ 207 , 208 ]."
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"Indeed, our 4N1K bi-peptides were 50-fold more efficient than mono-peptides to antagonize the effect of HTRA1 in the culture, confirming that the separation of the VVM sites by HTRA1 is likely suffici[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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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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"Activation of CD47 by TSP-1 increases macrophage IL-1β production, whereas monocytes lacking the receptor have muted IL-1β activation [111] ."
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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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"The proposed mechanism involves subretinal accumulation of mononuclear phagocytes due to the blockade of TSP1-dependent CD47 activation."
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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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"Activation of CD47 by TSP-1 increases macrophage IL-1β production, whereas monocytes lacking the receptor have muted IL-1β activation [111] ."
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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."
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"TSP1 activation of CD47 expressed on subretinal MPs triggers their RPE-induced elimination ( Calippe et al., 2017 )."
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"54 TSP1-mediated triggering of CD47 also inhibits the development of naive T cells into Th1 effector cells."
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"This provided a mechanism to explain previous evidence that TSP1 induces a switch in red cell CD47 function from anti-phagocytic to pro-phagocytic [53]."
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"Alternatively, the C-terminal domain of TSP1 competes with SIRPα for binding to CD47 [56], suggesting that TSP1 competitively blocks inhibitory CD47/SIRPα signaling (Figure 2d)."
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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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"TSP1-Induced CD47 Activation Blocks VEGF-C–Stimulated Lymphangiogenic Signaling."
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"As a pathogenic factor, complement factor H binding with CD11b inhibits TSP1 activation of CD47, whilst inhibiting CD47-mediated MP removal."
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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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"TSP1 induced CD47 receptor activation 41 inhibits the NO signaling pathway."
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"Overall, our results pointed to TSP-1 activation of CD47 as central in the maintenance of subretinal immunosuppression."
28228282
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"The observation that TSP-1 blockade reversed the effect of CFH deficiency and that recombinant CFH blocked the effect of TSP-1 on subretinal MP elimination strongly suggested that CFH binding to CD11b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28228282
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"We showed that CFH favored MP accumulation by inhibiting their elimination mediated by TSP-1 activation of CD47."
28228282
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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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"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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"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."
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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."
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"TSP-1 triggering of CD47 is known to increase activated human T cells ' susceptibility to Fas mediated apoptosis [XREF_BIBR]."
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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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"Moreover, a previous study revealed that activation of CD47 by THBS1 can stimulate ROS production and promote vascular dysfunction by promoting oxidative stress [ xref ]."
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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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"For example, platelet derived TSP-1 can promote both thrombosis and vascular pathogenesis through its interaction with CD36 on circulating cells and CD47 in endothelial cells [ 47 , 76–78 ]."
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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."
22926077
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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
sparser
"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
"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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"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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"The matricellular protein Thrombospondin-1 (TSP-1) can also activate CD47 [ xref ]."
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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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"Picomolar concentrations of TSP1-activated CD47 [33], suggesting that this interaction dominates under most conditions."
37217603
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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]."
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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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"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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"TSP-1 can activate CD47 on macrophages, affecting pro-inflammatory IL-1β maturation, a critical process for pathogen-induced and metabolic dysregulation-induced inflammation ( xref )."
38919018
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"Antibody blockade of TSP1 or morpholino suppression of CD47 dramatically enhanced survival of random tissue flaps."
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"Intriguingly, in young muscles undergoing hypertrophy in response to mechanical stress, thrombospondin-1/CD47 signaling induced by an exogenous thrombospondin-1 peptide was found to promote MuSC proliferation via a mechanism that requires calcitonin receptor downregulation and is independent of cAMP ."
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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."
21168495
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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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"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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"CD47 Independent Effects Mediated by the TSP Derived 4N1K Peptide."
24848268
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"The matricellular protein Thrombospondin-1 (TSP-1) can also activate CD47 [106]."
39194679
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"Persistent, high levels of intramuscular THBS1 and low levels of CD47 expression on the MuSCs' surface might cause the formation of large clusters of CD47 at the receptor level that are necessary to c[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
36459961
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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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"We recently demonstrated that TSP-1 activation of CD47 sensitizes infiltrating subretinal MPs to RPE induced death and elimination [ xref , xref ]."
35054863
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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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"TSP-1 activates CD47 and was reported to decrease the porosity through activation of the Rho-ROCK pathway."
36077249
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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 ]."
35054863
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"In addition, it has been proposed that inflammatory cell-derived factor H binds to CD11b, which causes a decrease in the elimination of inflammatory cells by blocking the thrombospondin-1 activation o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Interestingly, in a series of studies David Roberts’ group reported that blocking CD47 signaling induced by the CD47 ligand thrombospondin-1, or suppressing CD47 expression, protects normal tissues from IR injury while sensitizing the tumor cells , suggesting CD47 in tumor cells is important for DNA-damage repair."
36882648
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"CD47 Activation by Thrombospondin-1 in Lymphatic Endothelial Cells Suppresses Lymphangiogenesis and Promotes Atherosclerosis."
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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]."
28178210
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"Overall, our results pointed to TSP-1 activation of CD47 as central in the maintenance of subretinal immunosuppression."
28228282
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"The observation that TSP-1 blockade reversed the effect of CFH deficiency and that recombinant CFH blocked the effect of TSP-1 on subretinal MP elimination strongly suggested that CFH binding to CD11b[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28228282
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"The studies also suggest CD47 activation by a TSP1 specific peptide may play a central role."
19643963
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"We showed that CFH favored MP accumulation by inhibiting their elimination mediated by TSP-1 activation of CD47."
28228282
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"TSP1-Induced CD47 Activation Blocks VEGF-C-Stimulated Lymphangiogenic Signaling."
37259865
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"CD47 activation by thrombospondin-1 in lymphatic endothelial cells suppresses lymphangiogenesis and promotes atherosclerosis Background : Thrombospondin-1 ( TSP1 ) , a well-known angiogenesis inhibitor , mediates differential effects via interacting with cell surface receptors including CD36 and CD47 ."
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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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"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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"In VSMCs, THBS1-mediated CD47 activation stimulates Nox1-derived reactive oxygen species production, which inhibits VSMC-dependent vasorelaxation and induces vascular dysfunction [70]."
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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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"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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"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."
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"In addition, it has been proposed that inflammatory cell-derived factor H binds to CD11b, which causes a decrease in the elimination of inflammatory cells by blocking the thrombospondin-1 activation o[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
28622910
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"We demonstrated that both major genetic AMD risk factors, the CFH H402 variant and a 10q26 haplotype, inhibit TSP1-mediated CD47 activation and MP elimination, promoting pathogenic inflammation [17, 18]."
36755326
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"Taken together, Figure 6, F and G, suggest a feedback loop where TGF-β1 promotes signaling by TSP1 through further activation of TGF-β1 and CD47 to drive mucosal wound repair."
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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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"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."
25634975
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"We previously showed that the homeostatic elimination of infiltrating MPs is dependent on Thrombospondin 1 (TSP1)-mediated activation of the CD47 receptor on MPs [17]."
36755326
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"In summary, our study reveals that pigment-containing MPs can form in the retina as seen here in aged Cd47 -mice similar to dermal melanophages previously described [28], independently of the TSP1-mediated CD47 pathway."
36755326
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"CD47 signaling induced by TSP1 regulates a variety of cellular responses including nitric oxide/cGMP signaling, autophagy, stem cell self-renewal, and metabolic responses of cells to stress (Soto-Pantoja et al. 2015)."
34841476
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"Our results demonstrated CD47 as a major TSP1 receptor in LEC compared with CD36, and knockdown of CD47 in LEC and treatment with CD47-blocking antibody prevented the effects of TSP1 on lymphangiogenesis."
37259865
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"We recently showed that both major genetic AMD risk factors, the CFH H402 variant and a 10q26 haplotype, inhibit TSP1-mediated CD47 activation and subretinal MP elimination, promoting pathogenic inflammation [17, 18]."
36755326
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"Similarly, Gao et al reported that TSP1 accelerates brain endothelial cell senescence in a CD47-dependent manner."
37259865
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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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"TSP1 modulates interactions of CD47 with the exportin-1 complex."
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"TSP-1 activates CD47 and was reported to decrease the porosity through activation of the Rho-ROCK pathway."
36077249
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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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"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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"Increased TSP1 within the ECM could lead to increased CD47 activation thereby contributing to alphavbeta3-integrin-mediated CLAN formation in DEX treated HTM cells."
19643963
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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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"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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"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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