scholarly journals Fatty Acids, CD36, Thrombospondin-1, and CD47 in Glioblastoma: Together and/or Separately?

2022 ◽  
Vol 23 (2) ◽  
pp. 604
Author(s):  
Cristiana Tanase ◽  
Ana Maria Enciu ◽  
Elena Codrici ◽  
Ionela Daniela Popescu ◽  
Maria Dudau ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Matrix Protein ◽  
Cumulative Effect ◽  
Membrane Receptors ◽  
Extracellular Matrix Protein ◽  
Immunoglobulin Superfamily ◽  
Intratumor Heterogeneity ◽  
Brain Lipids ◽  
Wide Range ◽  
Thrombospondin 1

Glioblastoma (GBM) is one of the most aggressive tumors of the central nervous system, characterized by a wide range of inter- and intratumor heterogeneity. Accumulation of fatty acids (FA) metabolites was associated with a low survival rate in high-grade glioma patients. The diversity of brain lipids, especially polyunsaturated fatty acids (PUFAs), is greater than in all other organs and several classes of proteins, such as FA transport proteins (FATPs), and FA translocases are considered principal candidates for PUFAs transport through BBB and delivery of PUFAs to brain cells. Among these, the CD36 FA translocase promotes long-chain FA uptake as well as oxidated lipoproteins. Moreover, CD36 binds and recognizes thrombospondin-1 (TSP-1), an extracellular matrix protein that was shown to play a multifaceted role in cancer as part of the tumor microenvironment. Effects on tumor cells are mediated by TSP-1 through the interaction with CD36 as well as CD47, a member of the immunoglobulin superfamily. TSP-1/CD47 interactions have an important role in the modulation of glioma cell invasion and angiogenesis in GBM. Separately, FA, the two membrane receptors CD36, CD47, and their joint ligand TSP-1 all play a part in GBM pathogenesis. The last research has put in light their interconnection/interrelationship in order to exert a cumulative effect in the modulation of the GBM molecular network.

scholarly journals Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (12) ◽  
pp. 4548-4559 ◽  
Author(s):  
Mayumi Inoue ◽  
Yibin Jiang ◽  
Richard H. Barnes ◽  
Masakuni Tokunaga ◽  
Gabriel Martinez-Santibañez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Male Mice ◽  
High Fat ◽  
Adipose Tissues ◽  
Early Stages ◽  
Thrombospondin 1

Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression.

Hemicentin, a conserved extracellular member of the immunoglobulin superfamily, organizes epithelial and other cell attachments into oriented line-shaped junctions

Development ◽  
2001 ◽  
Vol 128 (6) ◽  
pp. 883-894 ◽  
Author(s):  
B.E. Vogel ◽  
E.M. Hedgecock
Keyword(s):  
Matrix Protein ◽  
Chromosome Instability ◽  
Basement Membranes ◽  
Extracellular Matrix Protein ◽  
Immunoglobulin Superfamily ◽  
Cell Contact ◽  
Chromosome Loss ◽  
Oriented Line ◽  
Escape Reflex ◽  
Epithelial Basement

him-4 mutations cause a novel syndrome of tissue fragility, defective cell migration and chromosome instability in Caenorhabditis elegans. Null mutants have abnormal escape reflex, mispositioning of the vas deferens and uterus, and mitotic chromosome loss and multinucleate cells in the germline. The him-4 gene product, hemicentin, is a conserved extracellular matrix protein with 48 tandem immunoglobulin repeats flanked by novel terminal domains. Secreted from skeletal muscle and gonadal leader cells, hemicentin assembles into fine tracks at specific sites, where it contracts broad regions of cell contact into oriented linear junctions. Some tracks organize hemidesmosomes in the overlying epidermis. Hemicentin tracks facilitate mechanosensory neuron anchorage to the epidermis, gliding of the developing gonad along epithelial basement membranes and germline cellularization.

scholarly journals Thrombospondin 1 mediates renal dysfunction in a mouse model of high-fat diet-induced obesity

2013 ◽  
Vol 305 (6) ◽  
pp. F871-F880 ◽  
Author(s):  
Wenpeng Cui ◽  
Hasiyeti Maimaitiyiming ◽  
Xinyu Qi ◽  
Heather Norman ◽  
Shuxia Wang
Keyword(s):  
Mouse Model ◽  
Renal Dysfunction ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Kidney Diseases ◽  
Extracellular Matrix Protein ◽  
Obese Mouse ◽  
Wild Type ◽  
Thrombospondin 1

Obesity is prevalent worldwide and is a major risk factor for many diseases including renal complications. Thrombospondin 1 (TSP1), a multifunctional extracellular matrix protein, plays an important role in diabetic kidney diseases. However, whether TSP1 plays a role in obesity-related kidney disease is unknown. In the present studies, the role of TSP1 in obesity-induced renal dysfunction was determined by using a diet-induced obese mouse model. The results demonstrated that TSP1 was significantly upregulated in the kidney from obese mice. The increased TSP1 was localized in the glomerular mesangium as well as in the tubular system from obese wild-type mice. Obese wild-type mice developed renal hypertrophy and albuminuria, which was associated with increased kidney macrophage infiltration, augmented kidney inflammation, and activated transforming growth factor (TGF)-β signaling and renal fibrosis. In contrast, obese TSP1-deficient mice did not develop these kidney damages. Furthermore, in vitro studies demonstrated that leptin treatment stimulated the expression of TSP1, TGF-β1, fibronectin, and collagen type IV in mesangial cells isolated from wild-type mice. These leptin-stimulated effects were abolished in TSP1-deficient mesangial cells. Taken together, these data suggest that TSP1 is an important mediator for obesity- or hyperleptinemia-induced kidney dysfunction.

scholarly journals Vascular smooth muscle cell growth arrest on blockade of thrombospondin-1 requires p21Cip1/WAF1

1999 ◽  
Vol 277 (3) ◽  
pp. H1100-H1106 ◽  
Author(s):  
Donghui Chen ◽  
Kun Guo ◽  
Jihong Yang ◽  
William A. Frazier ◽  
Jeffrey M. Isner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Matrix Protein ◽  
Molecular Mechanisms ◽  
Cellular Proliferation ◽  
Growth Arrest ◽  
Inhibitory Effect ◽  
Extracellular Matrix Protein ◽  
Inhibitory Protein ◽  
Thrombospondin 1

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is thought to play an important role in the pathogenesis of atherosclerosis and restenosis. Previous studies have implicated the extracellular matrix protein thrombospondin-1 (TSP1) in mitogen-dependent proliferation of VSMCs. In this study, we investigated the molecular mechanisms involved in TSP1-mediated regulation of VSMC growth. Neutralizing A4.1 anti-TSP1 antibody inhibited the activity of the G1/S cyclin-dependent kinase 2 (cdk2) and blocked the induction of S-phase entry, which normally occurs in serum-stimulated VSMCs. This growth-inhibitory effect was associated with a marked induction of p21Cip1/WAF1(p21) expression in A4.1-treated VSMCs. Moreover, addition of A4.1 antibody to VSMCs markedly increased the level of p21 bound to cdk2. Thus growth arrest on antibody blockade of TSP1 may be mediated by the cdk inhibitory protein p21. Consistent with this notion, anti-TSP1 antibody inhibited [3H]-thymidine incorporation in wild-type but not in p21-deficient mouse embryonic fibroblasts (MEFs). Together, these data suggest that p21 plays an important role in TSP1-mediated control of cellular proliferation.

scholarly journals Thrombospondin 1 and Its Diverse Roles as a Regulator of Extracellular Matrix in Fibrotic Disease

2019 ◽  
Vol 67 (9) ◽  
pp. 683-699 ◽  
Author(s):  
Joanne E. Murphy-Ullrich
Keyword(s):  
Extracellular Matrix ◽  
Stress Responses ◽  
Transforming Growth Factor Beta ◽  
Renal Fibrosis ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Extracellular Matrix Protein ◽  
Matrix Remodeling ◽  
Matrix Assembly ◽  
Thrombospondin 1

Thrombospondin 1 (TSP1) is a matricellular extracellular matrix protein that has diverse roles in regulating cellular processes important for the pathogenesis of fibrotic diseases. We will present evidence for the importance of TSP1 control of latent transforming growth factor beta activation in renal fibrosis with an emphasis on diabetic nephropathy. Other functions of TSP1 that affect renal fibrosis, including regulation of inflammation and capillary density, will be addressed. Emerging roles for TSP1 N-terminal domain regulation of collagen matrix assembly, direct effects of TSP1–collagen binding, and intracellular functions of TSP1 in mediating endoplasmic reticulum stress responses in extracellular matrix remodeling and fibrosis, which could potentially affect renal fibrogenesis, will also be discussed. Finally, we will address possible strategies for targeting TSP1 functions to treat fibrotic renal disease.

Lutheran blood group glycoprotein and its newly characterized mouse homologue specifically bind α5 chain-containing human laminin with high affinity

Blood ◽  
2001 ◽  
Vol 97 (1) ◽  
pp. 312-320 ◽  
Author(s):  
Stephen F. Parsons ◽  
Gloria Lee ◽  
Frances A. Spring ◽  
Thiebaut-Noel Willig ◽  
Luanne L. Peters ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Group ◽  
Sickle Cell ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Immunoglobulin Superfamily ◽  
Cell Disease ◽  
Amino Acid Sequence Level ◽  
High Affinity ◽  
Mouse Homologue

Abstract Lutheran blood group glycoproteins (Lu gps) are receptors for the extracellular matrix protein, laminin. Studies suggest that Lu gps may contribute to vaso-occlusion in sickle cell disease and it has recently been shown that sickle cells adhere to laminin isoforms containing the α5 chain (laminin 10/11). Laminin α5 is present in the subendothelium and is also a constituent of bone marrow sinusoids, suggesting a role for the Lu/laminin interaction in erythropoiesis. The objectives of the current study were to define more precisely the molecular interactions of the extracellular and intracellular regions of human Lu and to clone and characterize a mouse homologue. To this end, complementary DNA and genomic clones for the mouse homologue were sequenced and the mouse Lu gene mapped to a region on chromosome 7 with conserved synteny with human 19q13.2. Mouse and human Lu gps are highly conserved (72% identity) at the amino acid sequence level and both mouse and human Lu gps specifically bind laminin 10/11 with high affinity. Furthermore, the first 3, N-terminal, immunoglobulin superfamily domains of human Lu are critical for this interaction. The results indicated that the cytoplasmic domain of BRIC 221-labeled human Lu gp is linked with the spectrin-based skeleton, affording the speculation that this interaction may be critical for signal transduction. These results further support a role for Lu gps in sickle cell disease and indicate the utility of mouse models to explore the function of Lu gp-laminin 10/11 interaction in normal erythropoiesis and in sickle cell disease.

scholarly journals β1 Integrin Cytoplasmic Variants Differentially Regulate Expression of the Antiangiogenic Extracellular Matrix Protein Thrombospondin 1

2009 ◽  
Vol 69 (13) ◽  
pp. 5374-5382 ◽  
Author(s):  
Hira Lal Goel ◽  
Loredana Moro ◽  
Joanne E. Murphy-Ullrich ◽  
Chung-Cheng Hsieh ◽  
Chin-Lee Wu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Β1 Integrin ◽  
Thrombospondin 1

Evaluation of the thrombospondin-1 analogue ABT-510 in the APCMin/+ mouse intestinal adenoma model

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13545-13545 ◽  
Author(s):  
D. E. Joyce ◽  
G. Mulji ◽  
L. S. Gutierrez ◽  
F. J. Castellino
Keyword(s):  
Matrix Protein ◽  
Combined Treatment ◽  
Extracellular Matrix Protein ◽  
Rank Test ◽  
Tumor Vascularity ◽  
Angiogenic Switch ◽  
Treatment Groups ◽  
Significant Difference ◽  
Thrombospondin 1 ◽  
Intestinal Adenoma

13545 Background: The extracellular matrix protein Thrombospondin-1 (TSP-1) affects the angiogenic balance in cancer to suppress tumor growth. Exogenous TSP-1 or the peptide derivative ABT-510 (Abbott, Chicago, IL) can reverse this angiogenic switch from adenoma to carcinoma. We evaluated treatment effects of ABT-510 in the APCMin/+ mouse spontaneous intestinal adenoma model. This study determined reduction in intestinal adenoma number after ABT-510 or the combined treatment of ABT-510/bevacizumab (Genentech) compared to no treatment in APCMin/+. Proliferation, vascularity, and dysplasia were also compared. Methods: 90 day old APCMin/+ mice (familial adenomatous polyposis, 5q21 termination), Jackson Laboratory (Bar Harbor, ME)) received drug for three weeks: 1.) ABT-510, 60 mg/Kg/day s.c. pump for 2 weeks then i.p. daily for the last 7 days, 2.) Anti-VEGF antibody bevacizumab 10 mg/Kg i.p. twice per week in combination with ABT-510, and 3.) untreated controls. After 21 days mice were sacrificed, intestines harvested and adenomas enumerated. Immunohistochemistry (PCNA, vWF/CD31) was performed. Studies were IACUC approved. Wilcoxon signed-rank test was used to compare results. Results: Twenty one mice were evaluated with no adverse effects. Comparisons were made to untreated APCMin/+ controls. Untreated controls (N=7) demonstrated a mean of 7.7±1.25 polyps. ABT-510 treated APCMin/+ (N=8) demonstrated a mean of 3.4±1.8 polyps, significantly different from controls (p<0.004). Combined bevacizumab and ABT-510 treatment demonstrated a mean of 4.7 ±3.0 polyps (p<0.008). There was no significant difference between the ABT-510 and combined ABT-510/bevacizumab treated groups. Immunohistochemistry for tumor vascularity (anti-CD31/anti-vWF) and for proliferation (PCNA) demonstrated enhanced vascular and PCNA staining in polyps, but no differences were detected in tumor dysplasia or immunohistochemistry compared across control and treatment groups. Conclusions: Significant reduction in APCMin/+ polyp number was seen with ABT-510 and the combination ABT-510/bevacizumab treatment groups compared to untreated controls. Tumor-specific vascularity and proliferation was characteristically no different across control and treated groups. [Table: see text]

scholarly journals Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes

2011 ◽  
Vol 208 (5) ◽  
pp. 1083-1092 ◽  
Author(s):  
Claus Cursiefen ◽  
Kazuichi Maruyama ◽  
Felix Bock ◽  
Daniel Saban ◽  
Zahra Sadrai ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Corneal Neovascularization ◽  
Extracellular Matrix Protein ◽  
Vascular Endothelial ◽  
Monocytic Cells ◽  
Thrombospondin 1 ◽  
Corneal Lymphangiogenesis ◽  
Endothelial Growth Factor ◽  
Deficient Mice

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.

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