Tight junctions form the paracellular barrier for ions and uncharged solutes not only in "tight" but also in "leaky" epithelia. In the premolecular era of tight junction research, this was believed to be achieved in a perfect or less perfect way, depending mainly on the amount of horizontally oriented tight junction strands. During the past decade it emerged that tight junction molecules, such as claudin-1 and many others, strengthen the barrier, while a few claudins, such as claudin-2 or -10, weaken it. This report focuses on three claudins: one channel former and two barrier builders. Claudin-2 represents the prototype of a paracellular, channel-forming, tight junction protein responsible for specific transfer of solutes across the epithelium without entering the cells. This channel is selective for small cations but nearly impermeable to anions and uncharged solutes of any size. In contrast, claudin-5, a tight junction protein typical for all endothelia but also found in some epithelia, was characterized as a potent barrier builder. Claudin-8, another barrier builder, was demonstrated to be regulated by Na(+) uptake in surface epithelial cells of human colon. Here, aldosterone enhanced Na(+) absorption by dual action: transcellularly by inducing the epithelial sodium channel and paracellularly by preventing back leakage of absorbed Na(+) by upregulating claudin-8.
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http://dx.doi.org/10.1111/j.1749-6632.2009.04439.x | DOI Listing |
Toxicol Sci
January 2025
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas, 77843, USA.
Intestinal absorption is a key toxicokinetics parameter. While the colon carcinoma cell line Caco-2 is the most used in vitro model to estimate human drug absorption, models representing other intestinal segments are developed. We characterized the morphology, tissue-specific markers and functionality of three human intestinal cell types: Caco-2, primary human enteroid-derived cells from jejunum (J2), and duodenum (D109) when cultured in the OrganoPlate® 3-lane 40 microphysiological system (MPS) or static 24-well Transwells™.
View Article and Find Full Text PDFFront Microbiol
January 2025
Tianjin Key Laboratory of Conservation and Utilization of Animal Diversity, College of Life Sciences, Tianjin Normal University, Tianjin, China.
Background: Serovar Typhimurium (. Typhimurium) infection can cause inflammation and oxidative stress in the body, leading to gastroenteritis, fever and other diseases in humans and animals. More and more studies have emphasized the broad prospects of probiotics in improving inflammation and oxidative stress, but the ability and mechanism of (LA) to alleviate the inflammatory/oxidative reaction caused by pathogens are still unclear.
View Article and Find Full Text PDFCommun Biol
January 2025
Department of Histology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Tight junctions (TJs) between adjacent Sertoli cells are believed to form immunological barriers that protect spermatogenic cells expressing autoantigens from autoimmune responses. However, there is no direct evidence that Sertoli cell TJs (SCTJs) do indeed form immunological barriers. Here, we analyzed male mice lacking claudin-11 (Cldn11), which encodes a SCTJ component, and found autoantibodies against antigens of spermatocytes/spermatids in their sera.
View Article and Find Full Text PDFSci Rep
January 2025
School of Health Preservation and Rehabilitation, Chengdu University of TCM, Shierqiao Road, Chengdu, 610075, Sichuan, People's Republic of China.
Despite the established link between chronic high salt diet (HSD) and an increase in gut inflammation, the effect of HSD on the integrity of the intestinal barrier remains understudied. The present study aims to investigate the impact of HSD on the intestinal barrier in rats, encompassing its mechanical, mucous, and immune components. Expression levels of intestinal tight junction proteins and mucin-2 (MUC2) in SD rats were analyzed using immunofluorescence.
View Article and Find Full Text PDFDrug Metab Dispos
January 2025
Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington. Electronic address:
To further the development of an in vitro model that faithfully recapitulates drug disposition of orally administered drugs, we investigated the utility of human enteroid monolayers to simultaneously assess intestinal drug absorption and first-pass metabolism processes. We cultured human enteroid monolayers from 3 donors, derived via biopsies containing duodenal stem cells that were propagated and then differentiated atop permeable Transwell inserts, and confirmed transformation into a largely enterocyte population via RNA sequencing analysis and immunocytochemistry (ICC) assays. Proper cell morphology was assessed and confirmed via bright field microscopy and ICC imaging of tight junction proteins and other apically and basolaterally localized proteins.
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