China
Africa
Explore chapters and articles related to this topic
Endothelium
Published in Neil Herring, David J. Paterson, Levick's Introduction to Cardiovascular Physiology, 2018
Neil Herring, David J. Paterson
In an epithelium, a tight or ‘occludens’ junction forms close to a distinct, separate anchoring or ‘adherens’ junction. The endothelial junction contains proteins associated both with occludens-type junctions (claudin-5, occludin, junctional adhesion molecule, linker molecule ZO-1) and adherens-type junctions (vascular endothelial [VE]-cadherin, catenins) (Figure 9.3). VE-cadherin is a membrane-spanning glycoprotein whose extracellular domain binds to the VE-cadherin of the adjacent cell. Its intracellular domain binds to a complex of α, β and γ catenin, which is tethered by α-actinin to the junctional band of actin. A further junctional protein, platelet endothelial cell adhesion molecule (PECAM), promotes leukocyte emigration. The junctional complex is a dynamic structure that can be regulated rapidly via intracellular messengers. For example, agents that increase endothelial cyclic adenosine monophosphate (cAMP), such as isoprenaline, increase the number of junctional strands and thus reduce permeability. Conversely, during inflammation the phosphorylation of p-catenin and breakdown of junctional actin rapidly weaken the junction, leading to gap formation.
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
Soluble VE-cadherin is its extracellular domain shed through a metalloproteinase-dependent mechanism. Soluble VE-cadherin may potentially act as a competitive inhibitor of full-length VE-cadherin, as suggested by its inhibitory effect on tumor angiogenesis and tumor growth. According to one study on inflammatory skin conditions, vasculitis, vascular tumors, and normal controls, only psoriasis and atopic dermatitis were found to have low-serum-soluble VE-cadherin levels. Although VE-cadherin is an interesting candidate, with renewed interest in the angiogenesis field, not much clear data are available on the role of cadherins in angiogenesis associated with Ps or PsA.
Pulmonary Endothelium in Health and Viral Infections
Published in Sunit K. Singh, Human Respiratory Viral Infections, 2014
Nikolaos Manitsopoulos, Frantzeska Frantzeskaki, Anastasia Kotanidou, Stylianos E. Orfanos
The paracellular way refers to a route “around” the cell. The molecules that use this way are small, such as urea and glucose, and their transportation is size-selected, depending on their molecular radii (Mr), which cannot exceed 3 nm.1 The “continuous layer” of the endothelial structure is achieved through a complex set of junctional proteins forming tight junctions (TJs) and adherens junctions (AJs), giving shape to a zipper-like frame. Adherens junctions are formed mainly by vascular-endothelial (VE)-cadherin, a member of the cadherin family. These are single-span transmembrane glycoproteins. They mediate cell-to-cell adhesion in a calcium-dependent way.1 A potent disruptor of vascular permeability is vascular endothelial growth factor (VEGF). VE-cadherin maintains vascular permeability by binding to tyrosine kinase VEGF receptor 2 (VEGF-R2). In the presence of VEGF, the degradation of VE-cadherin is initiated and the AJs are disrupted.14,15 Tight junctions are formed by claudins, occluding and junctional adhesion molecules (JAMs). These three protein complexes bind zona occludens (ZO) to cytoplasmic signaling molecules and the actin cytoskeleton. AJs and TJs, composing the interendothelial junctions (IEJs) maintain vascular integrity via actin remodeling.1 Another type of connection between ECs is gap junctions (GJs). These are formed by hydrophilic transmembrane proteins called connexons (Cx), such as Cx37, Cx40, and CX43.1 Moreover, the paracellular pathway is affected by the interaction of ECs with ECM. Integrins are expressed by ECs and are bound to the ECM serving as protein receptors. The specific integrin binding sites of the ECM are named “focal contacts” or “focal adhesions.” Signaling pathways regulate paracellular permeability through a complex interaction between adhesive and counteradhesive forces, which adjust the opening and closing of the IEJs. The GJs signaling pathways also regulate the interactions between ECs and the ECM.1
A compound formulation of EGF-modified paclitaxel micelles and EGF-modified emodin micelles enhance the therapeutic effect of ovarian cancer
Published in Journal of Liposome Research, 2023
Ling Tang, Xiu-Xiu Liu, Xiao-Dan Yang, Shuang Tan, Zhong-Wen Zou
The process of cancer cell invasion and metastasis is inseparable from the regulation of protein. The hypoxic conditions of malignant tumors prevent HIF-α from being degraded (Foxler et al.2018). The high expression of HIF-α promotes the glycolysis of cancer cells and makes cancer cells more adaptable to the hypoxic microenvironment, and such a vicious cycle increases the growth rate and aggressiveness of cancer cells (Semenza 2019). When ovarian cancer metastasizes, it must penetrate the basement membrane rich in type IV collagen. MMP-2 and MMP-9 belong to the type IV collagenases and play an important role in degrading type IV collagen (Kessenbrock et al.2010). VE-Cadherin, a type of adhesion molecule specifically expressed in vascular endothelial cells, is essential in the process of blood vessel formation (Rochefort et al.2017). Studies have shown that VE-cadherin is associated with many malignant tumors angiogenesis and is a biomarker of certain tumor metastasis (Liu et al.2019). In this study, EGF-modified paclitaxel micelles plus EGF-modified emodin micelles downregulated HIF-α, MMP-2, MMP-9, and VE-cadherin, respectively, which not only confirmed the regulatory effects of emodin to invasion-related proteins, but once again proved the safety and superiority of EGF as a targeted molecule for ovarian cancer (Figure 7).
Cell-cell junctions: structure and regulation in physiology and pathology
Published in Tissue Barriers, 2021
Mir S. Adil, S. Priya Narayanan, Payaningal R. Somanath
E-cadherin, also known as classical cadherin,8 is expressed primarily in epithelial cells,35,46 and is associated with the AJs of the epithelial junctional complex. These structures altogether help the cells form a tight, polarized cell layer that can perform barrier and transport functions.46 It promotes the polarized epithelial phenotype which is essential to the stabilization of cell-to-cell adhesion. Loss of E-cadherin function is associated with the gain of invasiveness and metastatic potential of cells and, consequently, malignant transformation.8 VE-cadherin, like E-cadherin, is associated with the AJ junctions that help these cells to form transport barriers.46 These are the major transmembrane components of endothelial AJs,41,46,48 and are expressed in vivo in any type of vessels, arterial, venous and lymphatic. Its expression represents an early step in the differentiation of the endothelial phenotype.48 VE-cadherin has emerged as an adhesion molecule that plays essential roles in microvascular permeability and the morphogenic and proliferative events associated with angiogenesis.49 Therefore, the VE-cadherin knockout mouse died during embryonic development in past studies.41 N-cadherin and retinal (R)-cadherin are widely expressed in the nervous system and are associated with small adherens-type junctions at synapses, as well as at growth cones and other parts of the neuron.46
Impairment of lymphatic endothelial barrier function by X-ray irradiation
Published in International Journal of Radiation Biology, 2019
S. Anand Narayanan, John Ford, David C. Zawieja
Protein complexes between endothelial cells, for both blood and lymphatic endothelium, include adherens junctions that link to the intracellular cytoskeleton via actin. Adherens junctions consist of the transmembrane protein VE-cadherin, and intracellular protein components such as β-catenin (Lampugnani et al. 1995; Iyer et al. 2004; Di Lorenzo et al. 2013). VE-cadherin initiates intercellular contacts through trans-pairing between cadherins on opposing cells. β-catenin binds to the cytoplasmic domain of VE-cadherin, with actin consequently binding to β-catenin to link the adherens junction with the intracellular actin cytoskeletal arrangement. The lack of catenin association with VE-cadherin destabilizes VE-cadherin-mediated cell adhesion, which causes lack of cell-cell adhesion and leads to increases in endothelial permeability (Lampugnani et al. 1995; Iyer et al. 2004; Di Lorenzo et al. 2013). Whether there is impairment in cell-cell adhesion, and thus permeability function, of LECs upon exposure to ionizing radiation is unknown to date, a concern given the documented reports of cancer radiation therapy causing lymphedema as a side-effect that suggests impaired LEC barrier function (Mortimer et al. 1991; Rockson 2014).