Thromboxane stimulates synthesis of extracellular matrix proteins in vitro

1991 ◽  
Vol 261 (3) ◽  
pp. F488-F494 ◽  
Author(s):  
L. A. Bruggeman ◽  
E. A. Horigan ◽  
S. Horikoshi ◽  
P. E. Ray ◽  
P. E. Klotman
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Mesangial Cells ◽  
Extracellular Matrix Proteins ◽  
Cellular Protein ◽  
Matrix Proteins ◽  
Extracellular Matrix Protein ◽  
Renal Diseases ◽  
Glomerular Mesangial Cells

The vasoconstrictor eicosanoid thromboxane plays an important role in the pathogenesis of several renal diseases. As an autacoid, its local release alters blood flow and induces platelet aggregation. We report a direct stimulatory effect of thromboxane on extracellular matrix protein production and gene expression in vitro. Treatment of two cell types, differentiated mouse teratocarcinoma cells (F9+) and human glomerular mesangial cells, with two different thromboxane analogues resulted in increased production of components of the extracellular matrix including fibronectin and the basement membrane proteins laminin and type IV collagen. These responses to thromboxane were not the result of a mitogenic effect of thromboxane nor the result of an increase in total cellular protein. The increased production of extracellular matrix proteins was, at least in part, due to an increase in the steady-state level of mRNA for these genes. Furthermore, the effect of thromboxane was markedly inhibited by cotreatment with a thromboxane-receptor antagonist. These results suggest a new potential role for thromboxane as a mediator of the sclerotic and fibrotic responses to injury.

scholarly journals Localization of the Domains of the Haemophilus ducreyi Trimeric Autotransporter DsrA Involved in Serum Resistance and Binding to the Extracellular Matrix Proteins Fibronectin and Vitronectin

2008 ◽  
Vol 77 (2) ◽  
pp. 657-666 ◽  
Author(s):  
Isabelle Leduc ◽  
Bonnie Olsen ◽  
Christopher Elkins
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Haemophilus Ducreyi ◽  
Extracellular Matrix Protein ◽  
Serum Resistance ◽  
Passenger Domain ◽  
Normal Human ◽  
High Level

ABSTRACT Resisting the bactericidal activity of naturally occurring antibodies and complement of normal human serum is an important element in the evasion of innate immunity by bacteria. In the gram-negative mucosal pathogen Haemophilus ducreyi, serum resistance is mediated primarily by the trimeric autotransporter DsrA. DsrA also functions as an adhesin for the extracellular matrix proteins fibronectin and vitronectin and mediates attachment of H. ducreyi to keratinocytes. We sought to determine the domain(s) of the 236-residue DsrA protein required for serum resistance and extracellular matrix protein binding. A 140-amino-acid truncated protein containing only the C-terminal portion of the passenger domain and the entire translocator domain of DsrA exhibited binding to fibronectin and vitronectin and conferred serum resistance to an H. ducreyi serum-sensitive strain. A shorter DsrA construct consisting of only 128 amino acids was unable to bind to extracellular matrix proteins but was serum resistant. We concluded that neither fibronectin binding nor vitronectin binding is required for high-level serum resistance in H. ducreyi.

scholarly journals Purification and Partial Characterization of a Paracoccidioides brasiliensis Protein with Capacity To Bind to Extracellular Matrix Proteins

2005 ◽  
Vol 73 (4) ◽  
pp. 2486-2495 ◽  
Author(s):  
Angel González ◽  
Beatriz L. Gómez ◽  
Soraya Diez ◽  
Orville Hernández ◽  
Angela Restrepo ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Paracoccidioides Brasiliensis ◽  
Sodium Dodecyl ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Yeast Cells ◽  
Extracellular Matrix Protein ◽  
Dependent Manner ◽  
Fungal Propagules

ABSTRACT Microorganisms adhere to extracellular matrix proteins by means of their own surface molecules. Paracoccidioides brasiliensis conidia have been shown to be capable of interacting with extracellular matrix proteins. We aimed at determining the presence of fungal proteins that could interact with extracellular matrix protein and, if found, attempt their purification and characterization. Various extracts were prepared from P. brasiliensis mycelial and yeast cultures (total homogenates, β-mercaptoethanol, and sodium dodecyl sulfate [SDS] extracts) and analyzed by ligand affinity assays with fibronectin, fibrinogen and laminin. Two polypeptides were detected in both fungal forms. SDS extracts that interacted with all the extracellular matrix protein were tested; their molecular masses were 19 and 32 kDa. Analysis of the N-terminal amino acid sequence of the purified 32-kDa mycelial protein showed substantial homology with P. brasiliensis, Histoplasma capsulatum, and Neurospora crassa hypothetical proteins. Additionally, a monoclonal antibody (MAb) produced against this protein recognized the 32-kDa protein in the SDS extracts of both fungal forms for immunoblot. Immunofluorescence analysis revealed that this MAb reacted not only with mycelia and yeast cells, but also with conidia, indicating that this protein was shared by the three fungal propagules. By immunoelectron microscopy, this protein was detected in the cell walls and in the cytoplasm. Both the 32-kDa purified protein and MAb inhibited the adherence of conidia to the three extracellular matrix proteins in a dose-dependent manner. These findings demonstrate the presence of two polypeptides capable of interacting with extracellular matrix proteins on the surface of P. brasiliensis propagules, indicating that there may be common receptors for laminin, fibronectin, and fibrinogen. These proteins would be crucial for initial conidial adherence and perhaps also in dissemination of paracoccidioidomycosis.

scholarly journals Extracellular matrix protein N-glycosylation mediates immune self-tolerance in Drosophila melanogaster

2021 ◽  
Vol 118 (39) ◽  
pp. e2017460118
Author(s):  
Nathan T. Mortimer ◽  
Mary L. Fischer ◽  
Ashley L. Waring ◽  
Pooja KR ◽  
Balint Z. Kacsoh ◽  
...  
Keyword(s):  
Immune Response ◽  
Extracellular Matrix ◽  
Matrix Protein ◽  
Fat Body ◽  
Extracellular Matrix Proteins ◽  
Recognition System ◽  
Janus Kinase ◽  
Matrix Proteins ◽  
Extracellular Matrix Protein ◽  
Self Tolerance

In order to respond to infection, hosts must distinguish pathogens from their own tissues. This allows for the precise targeting of immune responses against pathogens and also ensures self-tolerance, the ability of the host to protect self tissues from immune damage. One way to maintain self-tolerance is to evolve a self signal and suppress any immune response directed at tissues that carry this signal. Here, we characterize the Drosophila tuSz1 mutant strain, which mounts an aberrant immune response against its own fat body. We demonstrate that this autoimmunity is the result of two mutations: 1) a mutation in the GCS1 gene that disrupts N-glycosylation of extracellular matrix proteins covering the fat body, and 2) a mutation in the Drosophila Janus Kinase ortholog that causes precocious activation of hemocytes. Our data indicate that N-glycans attached to extracellular matrix proteins serve as a self signal and that activated hemocytes attack tissues lacking this signal. The simplicity of this invertebrate self-recognition system and the ubiquity of its constituent parts suggests it may have functional homologs across animals.

Glomerular mesangial cell adhesion to fibrinogen is mediated by αvβ3 integrin

2004 ◽  
Vol 82 (5) ◽  
pp. 597-601 ◽  
Author(s):  
Edgar G Fischer
Keyword(s):  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Extracellular Matrix Proteins ◽  
Matrix Proteins ◽  
Biological Behavior ◽  
Αvβ3 Integrin ◽  
Glomerular Mesangial Cells ◽  
Mesangioproliferative Glomerulonephritis

The biological behavior of glomerular mesangial cells is thought to play a critical role in human and experimental forms of mesangioproliferative glomerulonephritis. In these diseases, mesangial cells proliferate and produce increased amounts of extracellular matrix proteins, which can lead to glomerulosclerosis and end-stage renal disease. Mesangial cells interact with extracellular matrix proteins through integrin-mediated cell adhesion. Fibrinogen as a plasma-derived protein is known to be deposited in the mesangium of kidneys affected by mesangioproliferative glomerulonephritis. The adhesive interactions between fibrinogen and mesangial cells, however, have not been reported. Results in this work show that mesangial cells adhere to immobilized fibrinogen in an integrin-dependent fashion. This process was inhibited by the αvβ3-selective peptide cyclo-RGDFV and the monoclonal anti-β3 integrin chain antibody F11. Ca2+ ions are a known strong inhibitor of the fibrinogen-αvβ3 interaction, and mesangial cell adhesion did not occur when Ca2+ was the only divalent cation present. Therefore, mesangial cell adhesion to fibrinogen is mediated by αvβ3 integrin, and divalent cations have a fundamental role in regulating this process.Key words: glomerular mesangial cells, adhesion, extracellular matrix, fibrinogen, integrins, αvβ3.

scholarly journals Signaling Mechanisms in the Regulation of Renal Matrix Metabolism in Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Meenalakshmi M. Mariappan
Keyword(s):  
Extracellular Matrix ◽  
Signaling Pathways ◽  
Matrix Protein ◽  
Structural Changes ◽  
Mammalian Target Of Rapamycin ◽  
Adverse Outcomes ◽  
Matrix Proteins ◽  
Extracellular Matrix Protein ◽  
Renal Hypertrophy ◽  
Matrix Metabolism

Renal hypertrophy and accumulation of extracellular matrix proteins are among cardinal manifestations of diabetic nephropathy. TGF beta system has been implicated in the pathogenesis of these manifestations. Among signaling pathways activated in the kidney in diabetes, mTOR- (mammalian target of rapamycin-)regulated pathways are pivotal in orchestrating high glucose-induced production of ECM proteins leading to functional and structural changes in the kidney culminating in adverse outcomes. Understanding signaling pathways that influence individual matrix protein expression could lead to the development of new interventional strategies. This paper will highlight some of the diverse components of the signaling network stimulated by hyperglycemia with an emphasis on extracellular matrix protein metabolism in the kidney in diabetes.

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