Search results for "Integrin"

2019

s2 integrin receptors consist of an alpha subunit (CD11a-CD11d) and CD18 as the common beta subunit, and are differentially expressed by leukocytes. s2 integrins are required for cell-cell interaction, transendothelial migration, uptake of opsonized pathogens, and cell signaling processes. Functional loss of CD18-termed leukocyte-adhesion deficiency type 1 (LAD1)-results in an immunocompromised state characterized by frequent occurrence of severe infections. In immunosuppressed individuals Aspergillus fumigatus is a frequent cause of invasive pulmonary fungal infection, and often occurs in patients suffering from LAD1. Here, we asked for the importance of CD11b/CD18 also termed MAC-1 which …

ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker.

2019

Abstract Alzheimer’s disease (AD) represents a global burden in the economics of healthcare systems. Amyloid-β (Aβ) peptides are formed by amyloid-β precursor protein (AβPP) cleavage, which can be processed by two pathways. The cleavage by the α-secretase A Disintegrin And Metalloprotease 10 (ADAM10) releases the soluble portion (sAβPPα) and prevents senile plaques. This pathway remains largely unknown and ignored, mainly regarding pharmacological approaches that may act via different signaling cascades and thus stimulate non-amyloidogenic cleavage through ADAM10. This review emphasizes the effects of natural compounds on ADAM10 modulation, which eventuates in a neuroprotective mechanism. M…

2018

We use the myotendinous junction of Drosophila flight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates …

Low density lipoprotein receptor-related protein 1 mediated endocytosis of β1-integrin influences cell adhesion and cell migration.

2015

The low density lipoprotein receptor-related protein 1 (LRP1) has been shown to interact with β1-integrin and regulate its surface expression. LRP1 knock-out cells exhibit altered cytoskeleton organization and decreased cell migration. Here we demonstrate coupled endocytosis of LRP1 and β1-integrin and the involvement of the intracellular NPxY2 motif of LRP1 in this process. Mouse embryonic fibroblasts harboring a knock in replacement of the NPxY2 motif of LRP1 by a multiple alanine cassette (AAxA) showed elevated surface expression of β1-integrin and decreased β1-integrin internalization rates. As a consequence, cell spreading was altered and adhesion rates were increased in our cell model…

2020

Orthodontic tooth movement (OTM) creates compressive and tensile strain in the periodontal ligament, causing circulation disorders. Hypoxia-inducible factor 1α (HIF-1α) has been shown to be primarily stabilised by compression, but not hypoxia in periodontal ligament fibroblasts (PDLF) during mechanical strain, which are key regulators of OTM. This study aimed to elucidate the role of heparan sulfate integrin interaction and downstream kinase phosphorylation for HIF-1α stabilisation under compressive and tensile strain and to which extent downstream synthesis of VEGF and prostaglandins is HIF-1α-dependent in a model of simulated OTM in PDLF. PDLF were subjected to compressive or tensile stra…

The Impact of Small Extracellular Vesicles on Lymphoblast Trafficking across the Blood-Cerebrospinal Fluid Barrier In Vitro.

2020

Central nervous System (CNS) disease in pediatric acute lymphoblastic leukemia (ALL) is a major concern, but still, cellular mechanisms of CNS infiltration are elusive. The choroid plexus (CP) is a potential entry site, and, to some extent, invasion resembles CNS homing of lymphocytes during healthy state. Given exosomes may precondition target tissue, the present work aims to investigate if leukemia-derived exosomes contribute to a permissive phenotype of the blood-cerebrospinal fluid barrier (BCSFB). Leukemia-derived exosomes were isolated by ultracentrifugation from the cell lines SD-1, Nalm-6, and P12-Ichikawa (P12). Adhesion and uptake to CP epithelial cells and the significance on sub…

Simultaneous Boron Ion‐Channel/Growth Factor Receptor Activation for Enhanced Vascularization

2018

[EN] Boron ion is essential in metabolism and its concentration is regulated by ion-channel NaBC1. NaBC1 mutations cause corneal dystrophies such as Harboyan syndrome. Here we propose a 3D molecular model for NaBC1 and show that simultaneous stimulation of NaBC1 and vascular growth factor receptors (VEGFR) promote angiogenesis in vitro and in vivo with ultra-low concentrations of VEGF. We show Human Umbilical Vein Endothelial Cells (HUVEC) organization into tubular structures indicative of vascularization potential. Enhanced cell sprouting was found only in the presence of VEGF and boron, effect abrogated after blocking NaBC1. We demonstrate that stimulated NaBC1 promotes angiogenesis via P…

Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system.

2018

Developing the bloodbrain barrier During development, signals need to be dynamically integrated by endothelial cells, neurons, and glia to achieve functional neuro-glia-vascular units in the central nervous system. During cortical development, neuronal Dab1 and ApoER2 receptors respond to a guidance cue called reelin. Studying mice, Segarra et al. found that Dab1 and ApoER2 are also expressed in endothelial cells (see the Perspective by Thomas). The integration of reelin signaling in endothelial cells and neurons facilitates the communication between vessels, glia, and neurons that is necessary for the correct positioning of neurons during cortical development. This integration is also impo…

The Commensal Microbiota Enhances ADP-Triggered Integrin αIIbβ3 Activation and von Willebrand Factor-Mediated Platelet Deposition to Type I Collagen

2020

The commensal microbiota is a recognized enhancer of arterial thrombus growth. While several studies have demonstrated the prothrombotic role of the gut microbiota, the molecular mechanisms promoting arterial thrombus growth are still under debate. Here, we demonstrate that germ-free (GF) mice, which from birth lack colonization with a gut microbiota, show diminished static deposition of washed platelets to type I collagen compared with their conventionally raised (CONV-R) counterparts. Flow cytometry experiments revealed that platelets from GF mice show diminished activation of the integrin αIIbβ3 (glycoprotein IIbIIIa) when activated by the platelet agonist adenosine diphosphate (ADP). Fu…

EGFL7 enhances surface expression of integrin α5β1 to promote angiogenesis in malignant brain tumors

2018

Abstract Glioblastoma (GBM) is a typically lethal type of brain tumor with a median survival of 15 months postdiagnosis. This negative prognosis prompted the exploration of alternative treatment options. In particular, the reliance of GBM on angiogenesis triggered the development of anti‐VEGF (vascular endothelial growth factor) blocking antibodies such as bevacizumab. Although its application in human GBM only increased progression‐free periods but did not improve overall survival, physicians and researchers still utilize this treatment option due to the lack of adequate alternatives. In an attempt to improve the efficacy of anti‐VEGF treatment, we explored the role of the egfl7 gene in ma…