L55	Endothelial cell-to-cell junctions.
E.Dejana
Department of Biomolecular and Biotechnological Sciences, Faculty of Sciences, Milan University and FIRC Institute of Molecular Oncology, Milan, IT.

Junctional structures maintain the integrity of the endothelium. Recent studies have shown that, as well as promoting cell–cell adhesion, junctions might transfer intracellular signals which regulate contact inhibition of growth, apoptosis, gene expression and new vessel formation. In general, junctions mediate stabilization signals and maintain the resting state of endothelial cells. These signals are attenuated and the junctions partially disorganized when endothelial cells migrate and proliferate, as occurs during the formation of new vessels. However, this process must be highly controlled. If junctions were fully dismantled, adverse effects — such as increase in apoptosis and uncontrolled cell proliferation — would prevail, leading to regression of newly formed vessels. Transgenic mice have been very informative in understanding the role of junctions in angiogenesis and vasculogenesis. Inactivation of genes coding for certain AJ proteins, such as VE-cadherin or b-catenin markedly inhibits normal vascular development in the embryo. By contrast, in the absence of certain TJ proteins, such as occludin, claudin-5, JAM-A, the vascular system can regularly form, but there are problems in the control of vascular permeability to fluids or circulating cells in the adult. Besides their role in proliferation and apoptosis, junctional proteins might be important in vascular tubulogenesis. During the development of the vascular system, endothelial cells form tubes by switching between a fibroblastoid/migratory state, in which they lack in large part apical–basal polarity, and an epithelioid state, in which they form intercellular junctions and establish an apical–lumenal surface. Junctions have a role in regulating cell polarity through rearrangement of the cytoskeleton and establishment of apical and basal surfaces that are required for lumen determination. Thus, modifications of the molecular organization and intracellular signaling of junctional proteins might have complex effects on vascular growth and stabilization.

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