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https://www.readbyqxmd.com/read/28636801/water-channels-and-barriers-formed-by-claudins
#1
REVIEW
Rita Rosenthal, Dorothee Günzel, Dian Theune, Carolina Czichos, Jörg-Dieter Schulzke, Michael Fromm
Physiological studies in leaky epithelia, like kidney proximal tubules and the small intestine, have documented water transport via both transcellular and paracellular pathways. The discovery of aquaporin water channels provided a molecular basis for transcellular water movement. In contrast, the contribution, or even existence, of a specific paracellular water pathway has been disputed for a long time, until the cation channel-forming tight junction protein claudin-2 was shown to also permit the paracellular passage of water through its pore...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28636798/a-ccpe-based-xenon-biosensor-for-magnetic-resonance-imaging-of-claudin-expressing-cells
#2
Anna Piontek, Christopher Witte, Honor May Rose, Miriam Eichner, Jonas Protze, Gerd Krause, Jörg Piontek, Leif Schröder
The majority of malignant tumors originate from epithelial cells, and many of them are characterized by an overexpression of claudins (Cldns) and their mislocalization out of tight junctions. We utilized the C-terminal claudin-binding domain of Clostridium perfringens enterotoxin (cCPE), with its high affinity to specific members of the claudin family, as the targeting unit for a claudin-sensitive cancer biosensor. To overcome the poor sensitivity of conventional relaxivity-based magnetic resonance imaging (MRI) contrast agents, we utilized the superior sensitivity of xenon Hyper-CEST biosensors...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28633471/development-of-a-chicken-ileal-explant-culture-model-for-measurement-of-gut-inflammation-induced-by-lipopolysaccharide
#3
Qian Zhang, Susan D Eicher, Kolapo M Ajuwon, Todd J Applegate
Gut mucosa holds a single layer of epithelial cells and the largest mass of lymphoid tissue in the body. Although the epithelial cell culture model is widely used to assess intestinal barrier function, it has limitations for studying cellular interactions, in particular those of the immune system. In this study, a chicken ileal explant culture model was developed for investigating short-term gut inflammatory and secretory responses in an ex vivo environment. Initially, ileal explants from broilers at 21 d of age were cultured ex vivo up to 6 h...
June 16, 2017: Poultry Science
https://www.readbyqxmd.com/read/28633196/tight-junction-strand-formation-by-claudin-10-isoforms-and-claudin-10a-10b-chimeras
#4
Susanne Milatz, Jörg Piontek, Caroline Hempel, Luca Meoli, Christoph Grohe, Anja Fromm, In-Fah M Lee, Rukeia El-Athman, Dorothee Günzel
Claudins are integral components of tight junctions (TJs) in epithelia and endothelia. When expressed in cell lines devoid of TJs, claudins are able to form TJ-like strands at contacts between adjacent cells. According to a current model of TJ strand formation, claudin protomers assemble in an antiparallel double row within the plasma membrane of each cell (cis-interaction) while binding to corresponding double rows from the neighboring cells (trans-interaction). Cis-interaction was proposed to involve two interfaces of the protomers' first extracellular segment (extracellular loop (ECL)1)...
June 20, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28633193/trictide-a-tricellulin-derived-peptide-to-overcome-cellular-barriers
#5
Jimmi Cording, Basak Arslan, Christian Staat, Sophie Dithmer, Susanne M Krug, Anneliese Krüger, Philipp Berndt, Ramona Günther, Lars Winkler, Ingolf E Blasig, Reiner F Haseloff
The majority of tight junction (TJ) proteins restrict the paracellular permeation of solutes via their extracellular loops (ECLs). Tricellulin tightens tricellular TJs (tTJs) and regulates bicellular TJ (bTJ) proteins. We demonstrate that the addition of recombinantly produced extracellular loop 2 (ECL2) of tricellulin opens cellular barriers. The peptidomimetic trictide, a synthetic peptide derived from tricellulin ECL2, increases the passage of ions, as well as of small and larger molecules up to 10 kDa, between 16 and 30 h after application to human epithelial colorectal adenocarcinoma cell line 2...
June 20, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28625129/triamcinolone-acetonide-suppresses-inflammation-and-facilitates-vascular-barrier-function-in-human-retinal-microvascular-endothelial-cells
#6
Shunsuke Imai, Tomohiro Otsuka, Akira Naito, Masamitsu Shimazawa, Hideaki Hara
BACKGROUND: Diabetic macular edema (DME) is resulted from the retinal microvascular leakage that accompanies the breakdown of blood-retinal barrier. Triamcinolone acetonide (TA) is a therapeutic agent for DME, but since the detailed mechanism of action of TA is not known, part of its action was examined. METHODS: In vitro model to enhance the permeability of human retinal microvascular endothelial cells (HRMECs) was constructed by using DME-related cytokines such as vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β)...
June 18, 2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/28623232/the-ring-finger-and-pdz-domain-containing-protein-pdzrn3-controls-localization-of-the-mg-2-regulator-claudin-16-in-renal-tube-epithelial-cells
#7
Kana Marunaka, Chisa Furukawa, Naoko Fujii, Toru Kimura, Takumi Furuta, Toshiyuki Matsunaga, Satoshi Endo, Hajime Hasegawa, Naohiko Anzai, Yasuhiro Yamazaki, Masahiko Yamaguchi, Akira Ikari
Ion exchange in the renal tubules is fundamental to the maintenance of physiological ion levels. Claudin-16 (CLDN16) regulates the paracellular reabsorption of Mg(2+) in the thick ascending limb of Henle's loop in the kidney, with dephosphorylation of CLDN16 increasing its intracellular distribution and decreasing paracellular Mg(2+) permeability. CLDN16 is located in the tight junctions, but the mechanism regulating its localization is unclear. Using yeast two-hybrid systems, we found that CLDN16 binds to PDZRN3, a protein containing both RING-finger and PDZ-domains...
June 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28618266/il-22%C3%A2-upregulates-epithelial-claudin-2-to-drive-diarrhea-and-enteric-pathogen-clearance
#8
Pei-Yun Tsai, Bingkun Zhang, Wei-Qi He, Juan-Min Zha, Matthew A Odenwald, Gurminder Singh, Atsushi Tamura, Le Shen, Anne Sailer, Sunil Yeruva, Wei-Ting Kuo, Yang-Xin Fu, Sachiko Tsukita, Jerrold R Turner
Diarrhea is a host response to enteric pathogens, but its impact on pathogenesis remains poorly defined. By infecting mice with the attaching and effacing bacteria Citrobacter rodentium, we defined the mechanisms and contributions of diarrhea and intestinal barrier loss to host defense. Increased permeability occurred within 2 days of infection and coincided with IL-22-dependent upregulation of the epithelial tight junction protein claudin-2. Permeability increases were limited to small molecules, as expected for the paracellular water and Na(+) channel formed by claudin-2...
June 14, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28617689/paracellular-transport-and-energy-utilization-in-the-renal-tubule
#9
Alan S L Yu
PURPOSE OF REVIEW: Paracellular transport across the tight junction is a general mechanism for transepithelial transport of solutes in epithelia, including the renal tubule. However, why paracellular transport evolved, given the existence of a highly versatile system for transcellular transport, is unknown. RECENT FINDINGS: Recent studies have identified the paracellular channel, claudin-2, that is responsible for paracellular reabsorption of sodium in the proximal renal tubule...
June 14, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28617312/autocrine-human-growth-hormone-promotes-invasive-and-cancer-stem-cell-like-behavior-of-hepatocellular-carcinoma-cells-by-stat3-dependent-inhibition-of-claudin-1-expression
#10
Yi-Jun Chen, Ming-Liang You, Qing-Yun Chong, Vijay Pandey, Qiu-Shi Zhuang, Dong-Xu Liu, Lan Ma, Tao Zhu, Peter E Lobie
Despite progress in diagnosis and treatment of hepatocellular carcinoma (HCC), the clinical outcome is still unsatisfactory. Increased expression of human growth hormone (hGH) in HCC has been reported and is associated with poor survival outcome in HCC patients. Herein, we investigated the mechanism of the oncogenic effects of hGH in HCC cell lines. In vitro functional assays demonstrated that forced expression of hGH in these HCC cell lines promoted cell proliferation, cell survival, anchorage-independent growth, cell migration, and invasion, as previously reported...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28614589/lactoferrin-protects-against-intestinal-inflammation-and-bacteria-induced-barrier-dysfunction-in-vitro
#11
Nina A Hering, Julia Luettig, Susanne M Krug, Stephanie Wiegand, Gabriele Gross, Eric A van Tol, Jörg D Schulzke, Rita Rosenthal
The iron-binding glycoprotein lactoferrin (LF) is naturally present in human breast milk. Several studies suggest that LF contributes to infant health and development owing to a variety of protective effects, including antimicrobial and anti-inflammatory features. Therefore, we aimed to elucidate its protective properties on intestinal epithelial barrier dysfunction induced by infection or inflammation using the human epithelial cell culture models HT-29/B6 and T84. During barrier perturbation induced by the proinflammatory cytokine tumor necrosis factor α (TNF-α), bovine LF restored tight junction (TJ) morphometry and inhibited TNF-α-induced epithelial apoptosis...
June 14, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28614588/architecture-of-the-paracellular-channels-formed-by-claudins-of-the-blood-brain-barrier-tight-junctions
#12
Flaviyan Jerome Irudayanathan, Nan Wang, Xiaoyi Wang, Shikha Nangia
Tight junctions (TJs) are key players in determining tissue-specific paracellular permeability across epithelial and endothelial membranes. Claudin proteins, the primary determinants of TJs structure and functionality, assemble in paracellular spaces to form channels and pores that are charge and size selective. Here, using molecular dynamics (MD) simulations, we elucidate the molecular assembly of claudin-3 and claudin-5 proteins of blood-brain barrier TJs. Despite having a high degree of sequence and structural similarity, these two claudins form different types of cis-interactions...
June 14, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28612843/tricellulin-is-regulated-via-interleukin-13-receptor-%C3%AE-2-affects-macromolecule-uptake-and-is-decreased-in-ulcerative-colitis
#13
S M Krug, C Bojarski, A Fromm, I M Lee, P Dames, J F Richter, J R Turner, M Fromm, J-D Schulzke
In the two inflammatory bowel diseases, ulcerative colitis (UC) and Crohn's disease (CD), altered expression of tight junction (TJ) proteins leads to an impaired epithelial barrier including increased uptake of luminal antigens supporting the inflammation. Here, we focused on regulation of tricellulin (Tric), a protein of the tricellular TJ essential for the barrier against macromolecules, and hypothesized a role in paracellular antigen uptake. We report that Tric is downregulated in UC, but not in CD, and that its reduction increases the passage of macromolecules...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28605828/crystal-structures-of-claudins-insights-into-their-intermolecular-interactions
#14
REVIEW
Hiroshi Suzuki, Kazutoshi Tani, Yoshinori Fujiyoshi
Claudins are four-transmembrane proteins that constitute the backbone of tight junction strands via self-polymerization in the apicolateral membranes of epithelial cells. Together with their cell-cell adhesion function, claudin proteins form the paracellular barrier and/or channels through epithelial cell sheets whose permeability is primarily dependent on the claudin subtype. Recently determined crystal structures of several claudins revealed the unique claudin fold of four transmembrane helices in a left-handed helical bundle with an extracellular β-sheet domain...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28605031/dynamic-modeling-of-the-tight-junction-pore-pathway
#15
Christopher R Weber, Jerrold R Turner
Claudins define paracellular permeability to small molecules by forming ion-selective pores within the tight junction. We recently demonstrated that claudin-2 channels are gated and open and close on a submillisecond timescale. To determine if and how the ensemble behavior of this unique class of entirely extracellular gated ion channels could define global epithelial barrier function, we have developed an in silico model of local claudin-2 behavior. This model considers the complex anastomosing ultrastructure of tight junction strands and can be scaled to show that local behavior defines global epithelial barrier function of epithelial monolayers expressing different levels of claudin-2...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28600680/tight-junctions-of-the-proximal-tubule-and-their-channel-proteins
#16
REVIEW
Michael Fromm, Jörg Piontek, Rita Rosenthal, Dorothee Günzel, Susanne M Krug
The renal proximal tubule achieves the majority of renal water and solute reabsorption with the help of paracellular channels which lead through the tight junction. The proteins forming such channels in the proximal tubule are claudin-2, claudin-10a, and possibly claudin-17. Claudin-2 forms paracellular channels selective for small cations like Na(+) and K(+). Independently of each other, claudin-10a and claudin-17 form anion-selective channels. The claudins form the paracellular "pore pathway" and are integrated, together with purely sealing claudins and other tight junction proteins, in the belt of tight junction strands surrounding the tubular epithelial cells...
June 9, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28598488/myosin-light-chain-kinase-knockout-improves-gut-barrier-function-and-confers-a-survival-advantage-in-polymicrobial-sepsis
#17
C Adam Lorentz, Zhe Liang, Mei Meng, Ching-Wen Chen, Benyam P Yoseph, Elise R Breed, Rohit Mittal, Nathan J Klingensmith, Alton B Farris, Eileen M Burd, Michael Koval, Mandy L Ford, Craig M Coopersmith
Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK(-/-) and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies...
June 7, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28596736/claudin-loss-of-function-disrupts-tight-junctions-and-impairs-amelogenesis
#18
Claire Bardet, Sandy Ribes, Yong Wu, Mamadou Tidiane Diallo, Benjamin Salmon, Tilman Breiderhoff, Pascal Houillier, Dominik Müller, Catherine Chaussain
Claudins are a family of proteins that forms paracellular barriers and pores determining tight junctions (TJ) permeability. Claudin-16 and -19 are pore forming TJ proteins allowing calcium and magnesium reabsorption in the thick ascending limb of Henle's loop (TAL). Loss-of-function mutations in the encoding genes, initially identified to cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), were recently shown to be also involved in Amelogenesis Imperfecta (AI). In addition, both claudins were expressed in the murine tooth germ and Claudin-16 knockout (KO) mice displayed abnormal enamel formation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28594555/effect-of-aging-on-the-absorption-of-small-peptides-in-spontaneously-hypertensive-rats
#19
Vu Thi Hanh, Weilin Shen, Mitsuru Tanaka, Aino E Siltari, Riita A Korpela, Toshiro Matsui
In the present study, we aimed to evaluate the effect of aging on the absorption of small peptides in spontaneously hypertensive rats (SHRs). Three kinds of dipeptides, glycyl-sarcosine (Gly-Sar), Trp-His, and captopril (a dipeptidomimetic drug), a Gly-Sar-Sar tripeptide, a Gly-Sar-Sar-Sar tetrapeptide, and a Gly-Sar-Sar-Sar-Sar pentapeptide were administered at doses of 10 mg/kg each to 8- and 40-week-old SHRs. The peptides were all detected in their intact forms in the blood. There was a significantly promoted absorption of di-/tripeptides in aged SHRs compared with young SHRs...
June 8, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28566578/functional-modulation-of-tight-junction-to-enhance-the-permeability-of-biological-products-biologics-in-biomembranes
#20
Yoshiteru Watanabe
 In recent years, biological products (biologics), including blood components, recombinant therapeutic proteins, antibodies, gene therapeutic materials, and so on, have been produced by biotechnology methods and other novel technologies. These products are essential therapeutic materials in progressive medicine. However, we often encounter the lower permeability of these biologics through biomembranes, due to their high molecular mass. In the last three decades, we have investigated drug delivery systems, including several enhancement methods for the permeability of biologics such as recombinant therapeutic proteins and viral vectors in epithelial cells...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
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