The blood–brain and gut–vascular barriers: from the perspective of claudins

Abstract

In some organs, such as the brain, endothelial cells form a robust and highly selective blood-to-tissue barrier. However, in other organs, such as the intestine, endothelial cells provide less stringent permeability, to allow rapid exchange of solutes and nutrients where needed. To maintain the structural and functional integrity of the highly dynamic blood–brain and gut–vascular barriers, endothelial cells form highly specialized cell-cell junctions, known as adherens junctions and tight junctions. Claudins are a family of four-membrane-spanning proteins at tight junctions and they have both barrier-forming and pore-forming properties. Tissue-specific expression of claudins has been linked to different diseases that are characterized by barrier impairment. In this review, we summarize the more recent progress in the field of the claudins, with particular attention to their expression and function in the blood–brain barrier and the recently described gut–vascular barrier, under physiological and pathological conditions. Abbreviations : 22q11DS 22q11 deletion syndrome; ACKR1 atypical chemokine receptor 1; AD Alzheimer disease; AQP aquaporin; ATP adenosine triphosphate; Aβ amyloid β; BAC bacterial artificial chromosome; BBB blood-brain barrier; C/EBP-α CCAAT/enhancer-binding protein α; cAMP cyclic adenosine monophosphate (or 3ʹ,5ʹ-cyclic adenosine monophosphate); CD cluster of differentiation; CNS central nervous system; DSRED discosoma red; EAE experimental autoimmune encephalomyelitis; ECV304 immortalized endothelial cell line established from the vein of an apparently normal human umbilical cord; EGFP enhanced green fluorescent protein; ESAM endothelial cell-selective adhesion molecule; GLUT-1 glucose transporter 1; GVB gut-vascular barrier; H2B histone H2B; HAPP human amyloid precursor protein; HEK human embryonic kidney; JACOP junction-associated coiled coil protein; JAM junctional adhesion molecules; LYVE1 lymphatic vessel endothelial hyaluronan receptor 1; MADCAM1 mucosal vascular addressin cell adhesion molecule 1; MAPK mitogen-activated protein kinase; MCAO middle cerebral artery occlusion; MMP metalloprotease; MS multiple sclerosis; MUPP multi-PDZ domain protein; PATJ PALS-1-associated tight junction protein; PDGFR-α platelet-derived growth factor receptor α polypeptide; PDGFR-β platelet-derived growth factor receptor β polypeptide; RHO rho-associated protein kinase; ROCK rho-associated, coiled-coil-containing protein kinase; RT-qPCR real time quantitative polymerase chain reactions; PDGFR-β soluble platelet-derived growth factor receptor, β polypeptide; T24 human urinary bladder carcinoma cells; TG2576 transgenic mice expressing the human amyloid precursor protein; TNF-α tumor necrosis factor α; WTwild-type; ZO zonula occludens.

Protective effect of homogeneous polysaccharides of Wuguchong (HPW) on intestinal mucositis induced by 5-fluorouracil in mice

“…However, intestinal homeostasis is a dynamic process between internal and external environments, and the apical junctional complex plays a crucial role in maintaining intestinal homeostasis, similar to intestinal epithelial cells. These tight junction proteins, including the representative transmembrane proteins Claudin and Occludin, bind endothelial cells together by means of scaffold proteins and actin, forming the mechanical barrier of the intestinal tract [ 35 ]. Claudins prevent the unlimited flow of water and solutes, as well as the invasion of luminal antigens [ 36 ].…”

Citrulline and long-term mortality in patients with cardiovascular disease

“…12 Finally, claudins are a highly diverse class of 27 proteins present in numerous tissues. 13 They have not only low tissue specificity but also opposing functions, making it difficult to choose a specific protein and interpret the results. 13 The usefulness of citrulline for the direct functional assessment of enterocyte mass has been confirmed in previous research studies.…”

“…1 The assessment of the intestinal barrier competency is a complex task which can be achieved using a number of approaches. 11 One approach is to use biomarkers such as bacterial lipopolysaccharide (LPS), 11 zonulin, 12 claudins, 13 and intestinal fatty acid binding protein. 14 There are also tools for evaluating the function of intestinal barrier samples such as the Ussing chamber.…”

Innate immune cell response to host-parasite interaction in a human intestinal tissue microphysiological system

“…The gut epithelium and vascular barrier regulate what enters the host tissue beyond the intestinal epithelial barrier and what enters the circulation. Functionally, the intestinal epithelial barrier separates the luminal contents from immune cells found in the gut parenchyma and prevents the systemic dissemination of the microbiota and enteric pathogens to the liver, spleen, and other peripheral tissues ( 3 ). During parasitic infection, immune cells in the gut parenchyma coordinate host-protective responses necessary for resolving acute infection and preventing tissue dissemination ( 4 ).…”