Search results for "INTEGRIN"
showing 10 items of 286 documents
Cleavage of endometrial α-integrins into their functional forms is mediated by proprotein convertase 5/6.
2012
Background Proprotein convertases (PCs) post-translationally activate a large number of protein precursors through limited cleavage. PC5/6 (PC6) in the human endometrium is tightly regulated during receptivity for embryo implantation. Integrins are transmembrane glycoproteins, some of which play an important role in the adhesive interactions between the trophoblast (blastocyst) and uterine epithelium at implantation. Integrins require PC cleavage for post-translational modification. We hypothesize that pro-integrin-αs in the endometrial epithelium are post-translationally cleaved by PC6 into functional subunits for the binding of blastocyst and adhesion of extracellular matrix proteins. Met…
αv-Class integrin binding to fibronectin is solely mediated by RGD and unaffected by an RGE mutation.
2020
Fibronectin (FN) is an essential glycoprotein of the extracellular matrix; binds integrins, syndecans, collagens, and growth factors; and is assembled by cells into complex fibrillar networks. The RGD motif in FN facilitates cell binding and fibrillogenesis through binding to α5β1 and αv-class integrins. However, whether RGD is the sole binding site for αv-class integrins is unclear. Most notably, substituting aspartate with glutamate (RGE) was shown to eliminate integrin binding in vitro, while mouse genetics revealed that FNRGE preserves αv-class integrin binding and fibrillogenesis. To address this conflict, we employed single-cell force spectroscopy, engineered cells, and RGD motif–defi…
The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease
2018
Commensal gut microbiota have recently been implicated in cardiovascular disease (CVD) and cerebrovascular disease. Atherosclerotic plaque formation depends on the colonization status of the host. In addition to host nutrition and the related microbiota-dependent metabolic changes, activation of innate immune pathways triggers the development of atherosclerosis and supports arterial thrombosis. Gnotobiotic mouse models have uncovered that activation of Toll-like receptor-2 by gut microbial ligands supports von Willebrand factor-integrin mediated platelet deposition to the site of vascular injury. Depending on nutritional factors, the microbiota-derived choline-metabolite trimethylamine N-ox…
The evolving role of platelets in inflammation.
2003
Platelets are small in size and simple in structure. Nevertheless, these anucleate cytoplasts utilize complex molecular systems to regulate a variety of biological functions. Here we review evolutionary paths, traditional roles, and previously unrecognized biological capacities of platelets that interface thrombosis with inflammation and potentially identify new roles in inflammatory diseases.
Novel α2β1 integrin inhibitors reveal that integrin binding to collagen under shear stress conditions does not require receptor preactivation.
2012
The interaction between α2β1 integrin (GPIa/IIa, VLA-2) and vascular collagen is one of the initiating events in thrombus formation. Here, we describe two structurally similar sulfonamide derivatives, BTT-3033 and BTT-3034, and show that, under static conditions, they have an almost identical effect on α2-expressing CHO cell adhesion to collagen I, but only BTT-3033 blocks platelet attachment under flow (90 dynes/cm(2)). Differential scanning fluorimetry showed that both molecules bind to the α2I domain of the recombinant α2 subunit. To further study integrin binding mechanism(s) of the two sulfonamides, we created an α2 Y285F mutant containing a substitution near the metal ion-dependent ad…
TREM-1 ligand expression on platelets enhances neutrophil activation
2007
Abstract The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important role in the innate immune response related to severe infections and sepsis. Modulation of TREM-1–associated activation improves the outcome in rodent models for pneumonia and sepsis. However, the identity and occurrence of the natural TREM-1 ligands are so far unknown, impairing the further understanding of the biology of this receptor. Here, we report the presence of a ligand for TREM-1 on human platelets. Using a recombinant TREM-1 fusion protein, we demonstrate specific binding of TREM-1 to platelets. TREM-1–specific signals are required for the platelet-induced augmentation of polymorphonuclear leu…
High-throughput elucidation of thrombus formation reveals sources of platelet function variability
2019
In combination with microspotting, whole-blood microfluidics can provide high-throughput information on multiple platelet functions in thrombus formation. Based on assessment of the inter-and intra-subject variability in parameters of microspot-based thrombus formation, we aimed to determine the platelet factors contributing to this variation. Blood samples from 94 genotyped healthy subjects were analyzed for conventional platelet phenotyping: i.e. hematologic parameters, platelet glycoprotein (GP) expression levels and activation markers (24 parameters). Furthermore, platelets were activated by ADP, CRP-XL or TRAP. Parallel samples were investigated for whole-blood thrombus formation (6 mi…
The first comprehensive and quantitative analysis of human platelet protein composition allows the comparative analysis of structural and functional …
2012
AbstractAntiplatelet treatment is of fundamental importance in combatting functions/dysfunction of platelets in the pathogenesis of cardiovascular and inflammatory diseases. Dysfunction of anucleate platelets is likely to be completely attributable to alterations in posttranslational modifications and protein expression. We therefore examined the proteome of platelets highly purified from fresh blood donations, using elaborate protocols to ensure negligible contamination by leukocytes, erythrocytes, and plasma. Using quantitative mass spectrometry, we created the first comprehensive and quantitative human platelet proteome, comprising almost 4000 unique proteins, estimated copy numbers for …
Overexpression of bone morphogenetic protein-6 (BMP-6) in the epidermis of transgenic mice: inhibition or stimulation of proliferation depending on t…
1996
Bone morphogenetic protein-6 (BMP-6) belongs to the family of TGF-beta-related growth factors. In the developing epidermis, expression of BMP-6 coincides with the onset of stratification. Expression persists perinatally but declines after day 6 postpartum, although it can still be detected in adult skin by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. We constitutively overexpressed BMP-6 in suprabasal layers of interfollicular epidermis in transgenic mice using a keratin 10 promoter. All mice expressing the transgene developed abnormalities in the skin, indicating an active transgene-derived factor. Depending on the pattern of transgene expression, the effects on proli…
Immunohistochemical Evaluation of Periodontal Regeneration Using a Porous Collagen Scaffold.
2021
(1) Aim: To immunohistochemically evaluate the effect of a volume-stable collagen scaffold (VCMX) on periodontal regeneration. (2) Methods: In eight beagle dogs, acute two-wall intrabony defects were treated with open flap debridement either with VCMX (test) or without (control). After 12 weeks, eight defects out of four animals were processed for paraffin histology and immunohistochemistry. (3) Results: All defects (four test + four control) revealed periodontal regeneration with cementum and bone formation. VCMX remnants were integrated in bone, periodontal ligament (PDL), and cementum. No differences in immunohistochemical labeling patterns were observed between test and control sites. N…