Search results for "INTEGRIN"

Concerted motions of the integrin-binding loop and the C-terminal tail of the non-RGD disintegrin obtustatin.

2003

Obtustatin is a potent and selective inhibitor of the alpha1beta1 integrin in vitro and of angiogenesis in vivo. It possesses an integrin recognition loop that harbors, in a lateral position, the inhibitory 21KTS23 motif. We report an analysis of the dynamics of the backbone and side-chain atoms of obtustatin by homonuclear NMR methods. Angular mobility has been calculated for 90 assigned cross-peaks from 22 off-resonance rotating frame nuclear Overhauser effect spectroscopy spectra recorded at three magnetic fields. Our results suggest that the integrin binding loop and the C-terminal tail display concerted motions, which can be interpreted by hinge effects. Among the integrin-binding moti…

2014

Oligodendrocytes are the myelinating glial cells of the central nervous system. In the course of brain development, oligodendrocyte precursor cells migrate, scan the environment and differentiate into mature oligodendrocytes with multiple cellular processes which recognize and ensheath neuronal axons. During differentiation, oligodendrocytes undergo dramatic morphological changes requiring cytoskeletal rearrangements which need to be tightly regulated. The non-receptor tyrosine kinase Fyn plays a central role in oligodendrocyte differentiation and myelination. In order to improve our understanding of the role of oligodendroglial Fyn kinase, we have identified Fyn targets in these cells. Pur…

Determining a healthy reference range and factors potentially influencing PRO-C3 – A biomarker of liver fibrosis

2021

Background & Aims Progressive fibrosis has been identified as the major predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). Several biomarkers are currently being evaluated for their ability to substitute the liver biopsy as the reference standard. Recent clinical studies in NAFLD/NASH patients support the utility of PRO-C3, a marker of type III collagen formation, as a marker for the degree of fibrosis, disease activity, and effect of treatment. Here we establish the healthy reference range, optimal sample handling conditions for both short- and long-term serum storage, and robustness for the PRO-C3 assay. Methods PRO-C3 was measured in 269 healthy volunteers…

Roles of molecules involved in epithelial/mesenchymal transition during angiogenesis

2007

Formation of vessels requires "epithelial-mesenchymal" transition of endothelial cells, with several modifications at the level of endothelial cell plasma membranes. These processes are associated with redistribution of cell-cell and cell-substrate adhesion molecules, cross talk between external ECM and internal cytoskeleton through focal adhesion molecules and the expression of several proteolytic enzymes, including matrix metalloproteases and serine proteases. These enzymes with their degradative action on ECM components, generate molecules acting as activators and/or inhibitors of angiogenesis. The purpose of this review is to provide an overview of the molecules involved in epithelial-m…

Profilin 1 is required for peripheral nervous system myelination

2014

Myelination allows rapid saltatory propagation of action potentials along the axon and is an essential prerequisite for the normal functioning of the nervous system. During peripheral nervous system (PNS) development, myelin-forming Schwann cells (SCs) generate radial lamellipodia to sort and ensheath axons. This process requires controlled cytoskeletal remodeling, and we show that SC lamellipodia formation depends on the function of profilin 1 (Pfn1), an actin-binding protein involved in microfilament polymerization. Pfn1 is inhibited upon phosphorylation by ROCK, a downstream effector of the integrin linked kinase pathway. Thus, a dramatic reduction of radial lamellipodia formation is obs…

Biochemical and structural comparison of spleen tyrosine kinase interaction with integrin and the immunoreceptor tyrosine-based activation motif

2019

Spleen tyrosine kinase (Syk) is a non-receptor tyrosine kinase involved in many different signalling pathways activated by immunoreceptors and integrins. The Syk activation mediated by phosphorylated Immunoreceptor Tyrosine-based Activation Motif (pITAM) receptors involves Src homology 2 (SH2) regulatory domains leading to Syk structural rearrangements. Differently, integrin cytoplasmic domains bind to the regulatory domain of Syk and the interaction does not require the phosphorylation, but the molecular mechanism is still unknown. This work focussed on describing the mechanism of integrin-Syk interaction and on how integrins activate Syk. First, using a fluorescent-based kinetic assay we …

Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts contain aggrecanase activity

2012

Membrane microvesicle shedding is an active process and occurs in viable cells with no signs of apoptosis or necrosis. We report here that microvesicles shed by oligodendroglioma cells contain an ‘aggrecanase’ activity, cleaving aggrecan at sites previously identified as targets for adamalysin metalloproteinases with disintegrin and thrombospondin domains (ADAMTSs). Degradation was inhibited by EDTA, the metalloproteinase inhibitor GM6001 and by tissue inhibitor of metalloproteinases (TIMP)-3, but not by TIMP-1 or TIMP-2. This inhibitor profile indicates that the shed microvesicles contain aggrecanolytic ADAMTS(s) or related TIMP-3-sensitive metalloproteinase(s). The oligodendroglioma cells…

Changes in the integrins expression are related with the osteoarthritis severity in an experimental animal model in rats

2014

We identify changes in the expression and localization of α5, α4, and α2 integrins during osteoarthritis (OA) pathogenesis in a rat experimental model. The changes were concomitant with variations in the extracellular matrix (ECM) content and the increase of metalloproteinases (MMPs) activity during OA pathogenesis, which were analyzed by immunofluorescence and Western blot assays. Our results showed an increased expression of α5 and α2 integrins at OA late stages, which was co-related with changes in the ECM content, as a consequence of the MMPs activity. In addition, this is the first report that has shown the presence of α4 integrin since OA early stages, which was co-related with the lo…

Transcriptome Analysis of Ullrich Congenital Muscular Dystrophy Fibroblasts Reveals a Disease Extracellular Matrix Signature and Key Molecular Regula…

2015

Background Collagen VI related myopathies encompass a range of phenotypes with involvement of skeletal muscle, skin and other connective tissues. They represent a severe and relatively common form of congenital disease for which there is no treatment. Collagen VI in skeletal muscle and skin is produced by fibroblasts. Aims & Methods In order to gain insight into the consequences of collagen VI mutations and identify key disease pathways we performed global gene expression analysis of dermal fibroblasts from patients with Ullrich Congenital Muscular Dystrophy with and without vitamin C treatment. The expression data were integrated using a range of systems biology tools. Results were validat…

Bone Metastasis in Renal Cell Carcinoma is Preprogrammed in the Primary Tumor and Caused by AKT and Integrin α5 Signaling

2015

Bone metastasis develops in 30% of all patients with renal cell carcinoma. We elucidated the mechanisms that lead to and predict bone metastasis of renal cell carcinoma.Nine renal cell carcinoma primary cell lines and 30 renal cell carcinoma tissue specimens (normal and tumor tissue) were collected from 3 patients with no metastasis and 10 with lung or bone metastasis within 5 years after nephrectomy. Cell migration was analyzed in a Boyden chamber and proliferation was assessed by bromodeoxyuridine incorporation. Adhesion to fibronectin, and collagen I and IV was determined after cell staining. The expression and/or activity of cellular signaling molecules was quantified by Western blot.Co…