ENDO ADHESION · Regulation of ensothelial barrier properties through activation of Rho family GTPases
6РП — Действия „Мария Кюри“
- Период
- 2005-10-01 → 2007-09-30
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Ендотелните клетки и техните връзки се анализират, за да се разбере как протеини като VE-cadherin и Cdc42 регулират пропускливостта на кръвните съдове. Това помага за разбирането на механизмите при възпаления, тромбози и атеросклероза.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - ENDO ADHESION (Regulation of ensothelial barrier properties through activation of Rho family GTPases)
The present study aims to elucidate signalling mechanisms residing at the cell-cell junctions of endothelial cells and especially at the adherens junctions. Adherens structures depend on transmembrane molecules called cadherins. Cadherins are cell-cell adhesion receptors that interact in homophilic fashion to connect cells of the same type. Adherens junction proteins include the armadillo repeat proteins b-catenin and p120 and actin associated proteins a-catenin, a-actinin and vinculin and others. We studied the properties of adherens junctions molecules using endothelial cells as a model system, because of the dynamic character of their junctions. Endothelial barrier function is dependent on VE-cadherin, an endothelial specific cadherin. Regulation of endothelial barrier function is an important property of the endothelium required for migration of salutes and cells from blood to tissues. Cadherin proteins are involved in serious diseases like atherosclerosis, inflammation and thrombosis. We examine the role of VE-cadherin in signalling and participation of actin rearrangement during cell-cell disruption mediated by the actin remodelling protein Cdc42. We also investigate the topology of VE-cadherin in the plasma membrane and we come to conclusion that its topology at the plasma membrane depends on a specialized lipid microenvironment that includes the Phosphatidyl-Inositol-phosphate (PIP2).
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Endothelium is a dynamic orhan with secretory and immunological functions that plays a key role in homeostasis, thrombosis and inflammation. Endothelial cells create a continuous monolayer lining blood vessels, semi-permeable to macromolecules, salutes and liquid, highly regulated by blood-born mediators.The endothelial barrier function is critically dependent on the integrity of cell-cell adhesion structures, especially the tight junctions and the adherens junctions (AJ). Endothelial AJ associates with acti n cytoskeleton and link neighbouring cells through the transmembrane VE-cadherin (Vascular Endothelial cadherin), the molecule that constitutes the backbone of AJ. Studies have shown that disassembly of AJ is an essential feature of the increased endothelial permeability response.Endothelial AJ are dynamic structures which respond to inflammatory mediators and thus modify their adhesion strength and alter endothelial barrier function. Cell-cell adhesion strength is regulated by: a) the extracellular cadherin repeats domain, and b) the cadherin cytoplasmic domain where p120- and b-catenins bind.These molecules function as essential linkers between cadherin and the actin cytoskeleton, which is requirement for strong cell-cell adhesion. Proinflammatory mediators such as thrombin, histamine and bradykinin activate their endothelial surface receptors and induce increased endothelial permeability responses through second messengers activation. In such cases endothelial cell-cell adhesion mediated by AJ is modulate d from strong to weak.The proposed studies aim to explore mechanisms responsible for reversal of the permeability increase and barrier recovery. We will study how endothelial adhesive structures and the associated cytoskeleton regulate barrier function. Specifically how adherens junctions participate in the reformation of endothelial junctions after the administration of pro-inflammatory agents.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITY OF IOANNINA · IOANNINAКоординаторНиво градГърция
Връзки
Данни: CORDIS, © Европейски съюз