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Integrin alpha 7

Neal M Rao, Joseph Capri, Whitaker Cohn, Maram Abdaljaleel, Lucas Restrepo, Jeffrey A Gornbein, William H Yong, David S Liebeskind, Julian P Whitelegge
INTRODUCTION: The specific protein composition of stroke-causing emboli is unknown. Because ischemic stroke has a varied etiology, it is possible that the composition of the thrombus from which an embolus originated will have distinctive molecular characteristics reflective of the underlying pathophysiology. We used mass spectrometry to evaluate the protein composition of retrieved emboli from patients with differing stroke etiologies and correlated the protein levels to serum predictors of atherosclerosis...
2017: Frontiers in Neurology
Nina Sarah Gowert, Meike Klier, Maria Reich, Friedrich Reusswig, Lili Donner, Verena Keitel, Dieter Häussinger, Margitta Elvers
BACKGROUND/AIMS: Platelets are essential mediators of hemostasis to avoid excessive blood loss. Cirrhosis and chronic liver diseases are characterized by alterations in hemostasis. Alterations in the secondary hemostasis have been well studied, while defects in primary hemostasis, especially the consequences of cholestatic liver disease on platelet function are not well defined. METHODS: After bile duct ligation (BDL) platelet activation and thrombus formation were analyzed in mice...
2017: Cellular Physiology and Biochemistry
Adam Nowakowski, Anna Andrzejewska, Johannes Boltze, Franziska Nitzsche, Li-Li Cui, Jukka Jolkkonen, Piotr Walczak, Barbara Lukomska, Miroslaw Janowski
Mesenchymal stem cells (MSCs) represent promising resource of cells for regenerative medicine in neurological disorders. However, efficient and minimally invasive methods of MSCs delivery to the brain still have to be developed. Intra-arterial route is very promising, but MSCs are missing machinery for diapedesis through blood-brain barrier. Thus, here we have tested a mRNA-based method to induce transient expression of ITGA4, an adhesion molecule actively involved in cell extravasation. We observed that transfection with an ITGA4-mRNA construct bearing a conventional cap analogue (7-methylguanosine) failed to produce ITGA4 protein, but exogenous ITGA4-mRNA was detected in transfected MSCs...
April 24, 2017: Scientific Reports
Yuan Jiang, Jinlu Dai, Zhi Yao, Greg Shelley, Evan T Keller
Integrins that contain an integrin αV subunit contribute to multiple functions that promote cancer progression. The goal of this study was to determine whether abituzumab (DI17E6, EMD 525797), a humanized monoclonal antibody (mAb) against integrin αV impacts, prostate cancer progression. To evaluate this, prostate cancer cells were treated with DI17E6 and its effects on proliferation, apoptosis, cell-cycle, adhesion, detachment, migration, invasion and phosphorylation of downstream targets, including FAK, Akt, and ERK, were determined...
July 2017: Molecular Cancer Research: MCR
E Thomas Pashuck, Benoît J R Duchet, Catherine S Hansel, Stephanie A Maynard, Lesley W Chow, Molly M Stevens
Cells in the body use a variety of mechanisms to ensure the specificity and efficacy of signal transduction. One way that this is achieved is through tight spatial control over the position of different proteins, signaling sequences, and biomolecules within and around cells. For instance, the extracellular matrix protein fibronectin presents RGDS and PHSRN sequences that synergistically bind the α5β1 integrin when separated by 3.2 nm but are unable to bind when this distance is >5.5 nm.1 Building biomaterials to controllably space different epitopes with subnanometer accuracy in a three-dimensional (3D) hydrogel is challenging...
December 27, 2016: ACS Nano
Nicolas Williet, Gilles Boschetti, Marion Fovet, Thomas Di Bernado, Pierre Claudez, Emilie Del Tedesco, Camille Jarlot, Leslie Rinaldi, Anne Berger, Jean-Marc Phelip, Bernard Flourie, Stéphane Nancey, Stéphane Paul, Xavier Roblin
BACKGROUND & AIMS: We investigated whether serum trough levels of vedolizumab, a humanized monoclonal antibody against integrin α4β7, during the induction phase of treatment can determine whether patients will need additional doses (optimization of therapy) within the first 6 months. METHODS: We conducted an observational study of 47 consecutive patients with Crohn's disease (CD; n = 31) or ulcerative colitis (UC; n = 16) who had not responded to 2 previous treatment regimens with antagonists of tumor necrosis factor and were starting therapy with vedolizumab at 2 hospitals in France, from June 2014 through April 2016...
November 2017: Clinical Gastroenterology and Hepatology
Carolijn Smids, Carmen S Horjus Talabur Horje, Femke van Wijk, Ellen G van Lochem
Monoclonal antibodies targeting integrins are emerging as new treatment option in inflammatory bowel diseases. Integrins are molecules involved in cell adhesion and signalling. After the successful introduction of anti-α4β7, currently anti-β7 is under evaluation in a phase three trial. Anti-β7 blocks both α4β7/MAdCAM-1 and αEβ7/E-cadherin interaction, targeting both the homing to and the retention in the gut of potential pathological T cells. Since the physiological and potential pathological roles of immune cells expressing αEβ7 are less distinct than of those expressing α4β7, an overview of the current state of knowledge on αEβ7 in mice and humans in both health and inflammatory bowel diseases is presented here, also addressing the potential consequences of anti-β7 treatment...
April 1, 2017: Journal of Crohn's & Colitis
Maira Estanislau S Almeida, Kelly S Monteiro, Ellen E Kato, Sandra C Sampaio, Tarcio T Braga, Niels O S Câmara, Marcelo L Lamers, Marinilce F Santos
Deficient wound healing is a common multifactorial complication in diabetic patients, but the cellular and molecular mechanisms involved are poorly defined. In the present study, we analyzed the effects of hyperglycemia on integrins expression in rat dermal fibroblasts and addressed its role in cell adhesion and migration. Diabetes Mellitus was induced in rats by streptozotocin injection and maintained for 30 days. Primary cultures of dermal fibroblasts from control and diabetic rats were maintained under low glucose (5 mM D-glucose) or high glucose (30 mM D-glucose) for 7 days...
October 2016: Molecular and Cellular Biochemistry
Annika Mutanen, Jouko Lohi, Timo Sorsa, Hannu Jalanko, Mikko P Pakarinen
BACKGROUND: Intestinal failure is associated frequently with liver injury, which persists after weaning off parenteral nutrition. We compared features of liver remodeling in intestinal failure during and after weaning off parenteral nutrition. METHODS: Liver biopsies and serum samples were obtained from 25 intestinal failure patients at a median age of 9.7 years (interquartile range: 4.6-18) and from age-matched control patients. Seven patients had been receiving parenteral nutrition for 53 months (22-160), and 18 patients had been weaned off parenteral nutrition 6...
September 2016: Surgery
Richard J Miron, Yuang Shuang, Dieter D Bosshardt, Jordi Caballé-Serrano, Fatiha Chandad, Yufeng Zhang
OBJECTIVES: Recently, novel biphasic calcium phosphate (BCP) scaffolds have emerged as a new class of bone grafts with osteoinductive potential demonstrating the ability to form ectopic bone in extra-skeletal sites. The aim of the present study was to perform an osteogenic gene array to target possible genes responsible for eliciting the changes in cell expression responsible for inducing osteoblast differentiation. MATERIALS AND METHODS: Human MG63 osteoblast-like cells were seeded for 24 h on tissue culture plastic or osteoinductive BCP particles and analyzed for upregulated genes using an osteogenesis super-array...
April 2017: Clinical Oral Investigations
Eugeni Domènech, Javier P Gisbert
Integrins play a crucial role in the development and maintenance of the inflammatory process in patients with inflammatory bowel disease. Vedolizumab is a humanized monoclonal antibody with a predominantly gastrointestinal effect. It specifically inhibits leukocyte integrin α4β7, thus preventing its interaction with mucosal vascular addressin cell adhesion molecule 1(MAdCAM-1), which is involved in the migration of lymphocytes from the blood stream to the intestinal tissue. Vedolizumab is indicated in the treatment of moderate to severe active Crohn's disease and ulcerative colitis in adult patients with poor response, loss of response, or intolerance to conventional treatment or to tumour necrosis factor alpha (TNF-α) antagonists...
December 2016: Gastroenterología y Hepatología
Ye Yuan, Larry Wu, Siqi Shen, Shiyong Wu, Monica M Burdick
AIMS: To determine the role of sialylation on α5β1 and α2β1 integrins in the regulation of adhesion between breast cancer cells and extracellular matrix (ECM). MAIN METHODS: Static cell adhesion assays were performed to quantify avidity of breast cancer cells to ECM. The effects of sialidases on α2,6 sialylation was assessed by flow cytometry using biotin conjugated Sambucus nigra lectin. Lectin affinity assays were used to determine expression of α2,6 sialylated integrins...
March 15, 2016: Life Sciences
L I Shen, Linbo Liu, Zhenyong Yang, Nan Jiang
The present study aimed to investigate the genes and signaling pathways associated with squamous cell carcinoma (SCC) by bioinformatics analysis. For this purpose, the GSE2503 was downloaded from the Gene Expression Omnibus database, and the differentially expressed genes (DEGs) between 6 normal skin and 5 SCC samples were analyzed using the Linear Models for Microarray Data package. Gene Ontology (GO) and pathway enrichment analysis of DEGs were performed, followed by functional annotation and construction of a protein-protein interaction (PPI) network...
February 2016: Oncology Letters
Qiao Hu, Xiao-Yan Wang, Li-Ke Kang, Hai-Ming Wei, Chun-Mei Xu, Tao Wang, Zong-Hua Wen
OBJECTIVE: To prepare arginine-glycine-aspartate (RGD)-targeted ultrasound contrast microbubbles (MBs) and explore the feasibility of their use in assessing dynamic changes in αvβ3 integrin expression in a murine model of tumor angiogenesis. METHODS: RGD peptides were conjugated to the surfaces of microbubbles via biotin-avidin linkage. Microbubbles bearing RADfK peptides were prepared as controls. The RGD-MBs were characterized using an Accusizer 780 and optical microscopy...
2016: PloS One
Nina K L Ma, Jia Kai Lim, Meng Fatt Leong, Edwin Sandanaraj, Beng Ti Ang, Carol Tang, Andrew C A Wan
A hierarchy of cellular stemness exists in certain cancers, and any successful strategy to treat such cancers would have to eliminate the self-renewing tumor-initiating cells at the apex of the hierarchy. The cellular microenvironment, in particular the extracellular matrix (ECM), is believed to have a role in regulating stemness. In this work, U251 glioblastoma cells are cultured on electrospun polystyrene (ESPS) scaffolds coated with an array of 7 laminin isoforms to provide a 3D model for stem cell-related genes and proteins expression studies...
February 2016: Biomaterials
Alexander Schwickert, Esther Weghake, Kathrin Brüggemann, Annika Engbers, Benjamin F Brinkmann, Björn Kemper, Jochen Seggewiß, Christian Stock, Klaus Ebnet, Ludwig Kiesel, Christoph Riethmüller, Martin Götte
MicroRNAs (miRNAs, micro ribonucleic acids) are pivotal post-transcriptional regulators of gene expression. These endogenous small non-coding RNAs play significant roles in tumorigenesis and tumor progression. miR-142-3p expression is dysregulated in several breast cancer subtypes. We aimed at investigating the role of miR-142-3p in breast cancer cell invasiveness. Supported by transcriptomic Affymetrix array analysis and confirmatory investigations at the mRNA and protein level, we demonstrate that overexpression of miR-142-3p in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells leads to downregulation of WASL (Wiskott-Aldrich syndrome-like, protein: N-WASP), Integrin-αV, RAC1, and CFL2, molecules implicated in cytoskeletal regulation and cell motility...
2015: PloS One
Gaik W Tew, Jason A Hackney, Deena Gibbons, Christopher A Lamb, Diana Luca, Jackson G Egen, Lauri Diehl, Jeff Eastham Anderson, Severine Vermeire, John C Mansfield, Brian G Feagan, Julian Panes, Daniel C Baumgart, Stefan Schreiber, Iris Dotan, William J Sandborn, John A Kirby, Peter M Irving, Gert De Hertogh, Gert A Van Assche, Paul Rutgeerts, Sharon O'Byrne, Adrian Hayday, Mary E Keir
BACKGROUND & AIMS: Etrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients with colon tissues that expressed high levels of the integrin αE gene (ITGAE) appeared to have the best response. We compared differences in colonic expression of ITGAE and other genes between patients who achieved clinical remission with etrolizumab vs those who did. METHODS: We performed a retrospective analysis of data collected from 110 patients with UC who participated in a phase 2 placebo-controlled trial of etrolizumab, as well as from 21 patients with UC or without inflammatory bowel disease (controls) enrolled in an observational study at a separate site...
February 2016: Gastroenterology
Onésia C Oliveira-Lima, Mauro C X Pinto, Johan Duchene, Fatimunnisa Qadri, Laura L Souza, Natalia Alenina, Michael Bader, Robson A S Santos, Juliana Carvalho-Tavares
Beyond the classical actions of the renin-angiotensin system on the regulation of cardiovascular homeostasis, several studies have shown its involvement in acute and chronic inflammation. The G protein-coupled receptor Mas is a functional binding site for the angiotensin-(1-7); however, its role in the immune system has not been fully elucidated. In this study, we evaluated the effect of genetic deletion of Mas receptor in lipopolysaccharide (LPS)-induced systemic and cerebral inflammation in mice. Inflammatory response was triggered in Mas deficient (Mas(-/-)) and C57BL/6 wild-type (WT) mice (8-12 weeks-old) by intraperitoneal injection of LPS (5 mg/kg)...
December 2015: Immunobiology
Armand G Ngounou Wetie, Kelly L Wormwood, Laci Charette, Jeanne P Ryan, Alisa G Woods, Costel C Darie
In the last decades, prevalence of autism spectrum disorder (ASD) has been on the rise. However, clear aetiology is still elusive and improvements in early diagnosis are needed. To uncover possible biomarkers present in ASD, we used two-dimensional polyacrylamide gel electrophoresis and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS), to compare salivary proteome profiling of children with ASD and controls. A total of 889 spots were compared and only those spots with a fold change ≥1.7 and a P-value <0...
November 2015: Journal of Cellular and Molecular Medicine
Young Wook Chun, Daniel A Balikov, Tromondae K Feaster, Charles H Williams, Calvin C Sheng, Jung-Bok Lee, Timothy C Boire, M Diana Neely, Leon M Bellan, Kevin C Ess, Aaron B Bowman, Hak-Joon Sung, Charles C Hong
Cardiomyocytes derived from human induced pluripotent stem cells (iPSC-CMs) hold great promise for modeling human heart diseases. However, iPSC-CMs studied to date resemble immature embryonic myocytes and therefore do not adequately recapitulate native adult cardiomyocyte phenotypes. Since extracellular matrix plays an essential role in heart development and maturation in vivo, we sought to develop a synthetic culture matrix that could enhance functional maturation of iPSC-CMs in vitro. In this study, we employed a library of combinatorial polymers comprising of three functional subunits - poly-ε-caprolacton (PCL), polyethylene glycol (PEG), and carboxylated PCL (cPCL) - as synthetic substrates for culturing human iPSC-CMs...
October 2015: Biomaterials
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