CDB15:0001462 THBS1 — CD36
Experimentally validated in Human, Mixed species, Mouse, Rat; Orthology-inferred in Human, Mouse, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep, Rat
Title
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Abstract
Activation of rat alveolar macrophage-derived latent transforming growth factor beta-1 by plasmin requires interaction with thrombospondin-1 and its cell surface receptor, CD36.
The American journal of pathology, 1999; PubMed, Rattus norvegicus Thbs1 — Rattus norvegicus Cd36
ABSTRACT: Transforming growth factor-beta-1 (TGF-beta1) is secreted by cells in a latent form (L-TGF-beta1) noncovalently bound to a latency-associated peptide. Activated alveolar macrophages obtained from rat lungs after bleomycin-induced pulmonary injury released increased amounts of active TGF-beta1 as well as plasmin, a protease, and thrombospondin-1 (TSP-1), a trimeric glycoprotein. Previously we had demonstrated that plasmin was critical to the activation of L-TGF- beta1. In the present study we demonstrated that TSP-1 is also important for the activation of L-TGF- beta1 because the activation can be inhibited by anti-TSP-1 monoclonal antibody. Proteins obtained from alveolar macrophage cell lysates immunoprecipitated with antibodies specific for TSP-1 were identified on immunoblots as LAP and TGF-beta1, indicating that TSP-1/L-TGF-beta1 complexes are present on alveolar macrophages. However, in the presence of plasmin both latency-associated peptide and TGF-beta1 were decreased in the same cell lysates, indicating that L-TGF-beta1 associated with TSP-1 is released by plasmin. Using immunofluorescence and antibodies to TGF-beta1 and CD36, a receptor for TSP-1, there was colocalization of TGF-beta1 with CD36. Because TSP-1 but not TGF-beta1 is a natural ligand for CD36, these findings suggest that the L-TGF-beta1 in a complex with TSP-1 localizes to the macrophage cell surface when TSP-1 interacts with its receptor, CD36. Furthermore, the association of TSP-1/L-TGF-beta1 complex with CD36 is necessary to the activation of L-TGF-beta1 because antibodies to CD36 prevent the colocalization of TGF-beta1 with CD36 as observed by immunofluorescence and inhibit activation of the L-TGF-beta1 by explanted alveolar macrophages. These findings suggest that activation of L-TGF-beta1 by plasmin occurs at the cell surface of activated alveolar macrophages and requires a TSP-1/CD36 interaction.
A CD36-binding peptide from thrombospondin-1 can stimulate resorption by osteoclasts in vitro.
Biochemical and biophysical research communications, 2000; PubMed, Homo sapiens THBS1 — Homo sapiens CD36
ABSTRACT: Thrombospondin-1 (TSP-1), purified from platelets, stimulates resorption by avian osteoclasts in an in vitro resorption assay. TSP-1 binds to a number of different cellular receptors via different domains of the molecule and several short receptor-binding sequences have been identified within the TSP-1 molecule. In this study, we have used synthetic peptides representing these various sequences in order to identify the cellular receptor and TSP domain responsible for stimulation of resorption. We show that one peptide CSVTCG, which represents the CD36-binding region of TSP-1, stimulates resorption in a fashion similar to the intact molecule, while the peptides RGDS, RFYVVMWK, and RFYVVM, representing other cell-binding domains of TSP, have no effect on resorption. Using RT-PCR and immunoblotting, we further demonstrate expression of CD36 in human osteoclastoma (giant cell tumour), primary human bone derived cells, and clonal osteoblastic cells. These studies suggest that CD36 is involved in regulation of resorption by osteoclasts and is the receptor responsible for the resorption-promoting effects of TSP-1.
Sense and antisense cDNA transfection of CD36 (glycoprotein IV) in melanoma cells. Role of CD36 as a thrombospondin receptor.
The Journal of biological chemistry, 1992; PubMed, Homo sapiens THBS1 — Homo sapiens CD36
ABSTRACT: Thrombospondin (TSP) is a multifunctional matrix and platelet glycoprotein that interacts with cell surfaces and may play a role in mediating cell adhesion, platelet aggregation, platelet-monocyte interactions, cell proliferation, angiogenesis, tumor metastasis, and protease generation. To clarify and confirm the function of CD36 (glycoprotein IV) as a TSP receptor, we now describe a transfected cell model using human melanoma cells genetically manipulated by sense or antisense cDNA transfection to express either high or near zero levels of CD36. Surface expression was confirmed by flow cytometry with monoclonal anti-CD36 IgG and quantified by measuring radiolabeled antibody binding. Bowes melanoma cells, which in their wild type did not express CD36 and did not bind radiolabeled TSP, when transfected with the sense construct bound TSP in a 1:1 stoichiometric ratio with CD36 expression. Conversely, C32 melanoma cells, which in their wild type expressed high levels of CD36 and bound radiolabeled TSP at a 1:1 stoichiometric ratio, did not express CD36 and did not bind TSP when transfected with an antisense construct. In addition, transfected Bowes cells and wild type C32 cells, unlike wild type Bowes cells, adhered to activated platelets in a TSP-dependent manner. These data, i.e. the gain of function with sense cDNA transfection and loss of function with antisense transfection, strongly support the TSP receptor function of CD36. The distribution of this protein in vascular cells and tissues and observations that it may participate in signal transduction events suggest that TSP-CD36 interactions may play a role in mediating some of the pathophysiological processes associated with TSP.
Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes.
The Journal of experimental medicine, 2011; PubMed, Homo sapiens THBS1 — Mus Musculus Cd36
ABSTRACT: Lymphangiogenesis plays an important role in tumor metastasis and transplant outcome. Here, we show that thrombospondin-1 (TSP-1), a multifunctional extracellular matrix protein and naturally occurring inhibitor of angiogenesis inhibits lymphangiogenesis in mice. Compared with wild-type mice, 6-mo-old TSP-1-deficient mice develop increased spontaneous corneal lymphangiogenesis. Similarly, in a model of inflammation-induced corneal neovascularization, young TSP-1-deficient mice develop exacerbated lymphangiogenesis, which can be reversed by topical application of recombinant human TSP-1. Such increased corneal lymphangiogenesis is also detected in mice lacking CD36, a receptor for TSP-1. In these mice, repopulation of corneal macrophages with predominantly WT mice via bone marrow reconstitution ameliorates their prolymphangiogenic phenotype. In vitro, exposure of WT macrophages to TSP-1 suppresses expression of lymphangiogenic factors vascular endothelial growth factor (VEGF)-C and VEGF-D, but not of a primarily hemangiogenic factor VEGF-A. Inhibition of VEGF-C is not detected in the absence or blockade of CD36. These findings suggest that TSP-1, by ligating CD36 on monocytic cells, acts as an endogenous inhibitor of lymphangiogenesis.
THBS1 regulates trophoblast fusion through a CD36-dependent inhibition of cAMP, and its upregulation participates in preeclampsia.
Genes & diseases, 2021; PubMed, Homo sapiens THBS1 — Homo sapiens CD36
ABSTRACT: Preeclampsia is a pregnancy complication which threatens the survival of mothers and fetuses. It originates from abnormal placentation, especially insufficient fusion of the cytotrophoblast cells to form the syncytiotrophoblast. In this study, we found that THBS1, a matricellular protein that mediates cell-to-cell and cell-to-matrix interactions, is downregulated during the fusion of primary cytotrophoblast and BeWo cells, but upregulated in the placenta of pregnancies complicated by preeclampsia. Also, THBS1 was observed to interact with CD36, a membrane signal receptor and activator of the cAMP signaling pathway, to regulate the fusion of cytotrophoblast cells. Overexpression of THBS1 inhibited the cAMP signaling pathway and reduced the BeWo cells fusion ratio, while the effects of THBS1 were abolished by a CD36-blocking antibody. Our results suggest that THBS1 signals through a CD36-mediated cAMP pathway to regulate syncytialization of the cytotrophoblast cells, and that its upregulation impairs placental formation to cause preeclampsia. Thus, THBS1 can serve as a therapeutic target regarding the mitigation of abnormal syncytialization and preeclampsia.