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Jia Li, Yang Zhao, Ying Lu, William Ritchie, Georges Grau, Mathew A Vadas, Jennifer R Gamble
The regulation of function of endothelial cell-cell junctions is fundamental in sustaining vascular integrity. The polycistronic microRNA (miR) complexes containing miR-23a-27a-24-2, and 23b-27b-24-1 are predicted to target the majority of major endothelial junctional proteins. We focus on miR-23a and miR-23b, and investigate the functional effects of these miRs on junctions. While miR-23a and 23b only differ by 1 nucleotide (g19) outside the seed region and thus are predicted to have the same targets, they function differently with miR-23a inhibiting permeability and miR-23b inhibiting angiogenesis...
August 23, 2016: Molecular Therapy. Nucleic Acids
Lei Wang, Yang Chen, Xiang Li, Youzhi Zhang, Erich Gulbins, Yang Zhang
Obesity is an important risk factor for exacerbating chronic diseases such as cardiovascular disease and cancer. High serum level of saturated free fatty acids such as palmitate is an important contributor for obesity-induced diseases. Here, we examined the contribution of inflammasome activation in vascular cells to free fatty acid-induced endothelial dysfunction and vascular injury in obesity. Our findings demonstrated that high fat diet-induced impairment of vascular integrity and enhanced vascular permeability in the myocardium in mice were significantly attenuated by Nlrp3 gene deletion...
September 28, 2016: Oncotarget
Bin Zhao, Xiaoke Wang, Jun Zheng, Hailiang Wang, Jun Liu
Considerable evidence has demonstrated that metformin can activate 5'-AMP-activated protein kinase (AMPK) signaling pathway, which plays a critical role in protection of endothelial cell permeability. Hence, the present study evaluated the effects of metformin on blood brain barrier permeability and AQP4 expression in vitro, and assessed the effects of metformin treatment on tumor-induced brain edema in vivo. Hypoxia or VEGF exposure enhanced bEnd3 endothelial cell monolayer permeability and attenuated the expression of tight junction proteins including Occludin, Claudin-5, ZO-1, and ZO-2...
2016: American Journal of Translational Research
Hui-Jun Xu, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) (1) increased reactive oxygen species, malondialdehyde and protein carbonyl (PC) contents (P < 0.05), decreased the copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and mRNA levels (P < 0...
September 15, 2016: Fish & Shellfish Immunology
Franziska Wetzel, Sonnhild Mittag, Misael Cano-Cortina, Tobias Wagner, Oliver H Krämer, Rainer Niedenthal, Lorenza Gonzalez-Mariscal, Otmar Huber
The zonula occludens (ZO)-2 protein links tight junctional transmembrane proteins to the actin cytoskeleton and associates with splicing and transcription factors in the nucleus. Multiple posttranslational modifications control the intracellular distribution of ZO-2. Here, we report that ZO-2 is a target of the SUMOylation machinery and provide evidence on how this modification may affect its cellular distribution and function. We show that ZO-2 associates with the E2 SUMO-conjugating enzyme Ubc9 and with SUMO-deconjugating proteases SENP1 and SENP3...
September 7, 2016: Cellular and Molecular Life Sciences: CMLS
Olga J Baker
Tight junctions form a continuous intercellular barrier between epithelial cells that is required to separate tissue spaces and regulate selective movement of solutes across the epithelium. They are composed of strands containing integral membrane proteins (e.g., claudins, occludin and tricellulin, junctional adhesion molecules and the coxsackie adenovirus receptor). These proteins are anchored to the cytoskeleton via scaffolding proteins such as ZO-1 and ZO-2. In salivary glands, tight junctions are involved in polarized saliva secretion and barrier maintenance between the extracellular environment and the glandular lumen...
July 2016: Tissue Barriers
Emma L Jenkins, Massimo Caputo, Gianni D Angelini, Mohamed T Ghorbel
AIMS: Tight junction protein zonula occludens protein 2 (ZO-2) is a member of the membrane-associated guanylate kinases protein family known to be expressed at tight junctions of epithelial and endothelial cells and at adherens junctions (AJs) in cardiomyocytes. Little is known about ZO-2 expression and function in the human heart. Here, we examined the hypothesis that chronic hypoxia down-regulates ZO-2 expression in human myocardium and cultured rat cardiomyocytes. METHODS AND RESULTS: Patients with a diagnosis of cyanotic (n = 10) or acyanotic (n = 10) Tetralogy of Fallot undergoing surgical repair were used to examine ZO-2 messenger RNA and protein expression by real time-PCR, immunohistochemistry, and western blotting...
June 2016: ESC Heart Failure
David Briskey, Mandy Heritage, Lesley-Anne Jaskowski, Jonathan Peake, Glenda Gobe, V Nathan Subramaniam, Darrell Crawford, Catherine Campbell, Luis Vitetta
BACKGROUND: We have investigated the effects of a multispecies probiotic preparation containing a combination of probiotic bacterial genera that included Bifidobacteria, Lactobacilli and a Streptococcus in a mouse model of high-fat diet or obesity-induced liver steatosis. METHODS: Three groups of C57B1/6J mice were fed either a standard chow or a high-fat diet for 20 weeks, while a third group was fed a high-fat diet for 10 weeks and then concomitantly administered probiotics for a further 10 weeks...
July 2016: Therapeutic Advances in Gastroenterology
Steve Schwartz, Emily Frank, Dennis Gierhart, Paula Simpson, Robert Frumento
BACKGROUND: Dietary modification, through supplementation and elimination diets, has become an area of interest to help slow skin aging, reduce symptom severity or prevent reoccurrence of certain dermatologic conditions [Clinical Dermatology vol. 31 (2013) 677-700]. Free radical components (reactive oxygen species or ROS) or lipid peroxide (LPO) is involved in the pathogenesis and progression of accelerated skin aging when prolonged oxidative stress occurs. The use of antioxidant-related therapies such as nutraceuticals is of particular interest in restoring skin homeostasis...
June 17, 2016: Journal of Cosmetic Dermatology
Wei Liu, Dong Hu, Haizhong Huo, Weifeng Zhang, Fatemeh Adiliaghdam, Sarah Morrison, Juan M Ramirez, Sarah S Gul, Sulaiman R Hamarneh, Richard A Hodin
BACKGROUND: Intestinal alkaline phosphatase (IAP) plays a pivotal role in maintaining gut health and well-being. Oral supplementation with IAP in mice improves gut barrier function and prevents luminal proinflammatory factors from gaining access to the circulation. In this study, we sought to explore the relationship between IAP and tight junction protein (TJP) expression and function. STUDY DESIGN: The effect of IAP deletion on TJP levels was studied in mouse embryonic fibroblasts (MEFs) generated from IAP-knockout and wild type mice...
June 2016: Journal of the American College of Surgeons
Gleb Martovetsky, Kevin T Bush, Sanjay K Nigam
The hepatocyte nuclear factors, Hnf1a and Hnf4a, in addition to playing key roles in determining hepatocyte fate, have been implicated as candidate lineage-determining transcription factors in the kidney proximal tubule (PT) [Martovetsky et. al., (2012) Mol Pharmacol 84:808], implying an additional level of regulation that is potentially important in developmental and/or tissue-engineering contexts. Mouse embryonic fibroblasts (MEFs) transduced with Hnf1a and Hnf4a form tight junctions and express multiple PT drug transporters (e...
July 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Wei Li, Kaiji Sun, Yun Ji, Zhenlong Wu, Weiwei Wang, Zhaolai Dai, Guoyao Wu
BACKGROUND: Glycine traditionally is classified as a nutritionally nonessential amino acid in humans and animals. Because of its abundance in the body and its extensive use via multiple pathways, requirements for glycine are particularly high in neonates. Our recent studies show that dietary glycine supplementation is needed for optimal intestinal development in piglets. Importantly, reduced concentrations of glycine in the lumen of the small intestine are associated with gut dysfunction in low-birth-weight piglets...
May 2016: Journal of Nutrition
Alaide Domínguez-Calderón, Antonia Ávila-Flores, Arturo Ponce, Esther López-Bayghen, José-Víctor Calderón-Salinas, José Luis Reyes, Bibiana Chávez-Munguía, José Segovia, Carla Angulo, Leticia Ramírez, Helios Gallego-Gutiérrez, Lourdes Alarcón, Dolores Martín-Tapia, Pablo Bautista-García, Lorenza González-Mariscal
Renal compensatory hypertrophy (RCH) restores normal kidney function after disease or loss of kidney tissue and is characterized by an increase in organ size due to cell enlargement and not to cell proliferation. In MDCK renal epithelial cells, silencing of the tight junction protein zona occludens 2 (ZO-2 KD) induces cell hypertrophy by two mechanisms: prolonging the time that cells spend at the G1 phase of the cell cycle due to an increase in cyclin D1 level, and augmenting the rate of protein synthesis. The latter is triggered by the nuclear accumulation and increased transcriptional activity of Yes-associated protein (YAP), the main target of the Hippo pathway, which results in decreased expression of phosphatase and tensin homologue...
May 15, 2016: Molecular Biology of the Cell
Rony Chidiac, Ying Zhang, Sylvain Tessier, Denis Faubert, Chantal Delisle, Jean-Philippe Gratton
VEGF and angiopoietin-1 (Ang-1) are essential factors to promote angiogenesis through regulation of a plethora of signaling events in endothelial cells (ECs). Although pathways activated by VEGF and Ang-1 are being established, the unique signaling nodes conferring specific responses to each factor remain poorly defined. Thus, we conducted a large-scale comparative phosphoproteomic analysis of signaling pathways activated by VEGF and Ang-1 in ECs using mass spectrometry. Analysis of VEGF and Ang-1 networks of regulated phosphoproteins revealed that the junctional proteins ZO-1, ZO-2, JUP and p120-catenin are part of a cluster of proteins phosphorylated following VEGF stimulation that are linked to MAPK1 activation...
May 2016: Molecular & Cellular Proteomics: MCP
Y Zhang, P Zheng, B Yu, J He, J Yu, X B Mao, J X Wang, J Q Luo, Z Q Huang, G X Cheng, D W Chen
The objective of this study was to evaluate the effects of dietary addition of spray-dried chicken plasma (SDCP) as a replacement for spray-dried porcine plasma (SDPP) on serum biochemistry, intestinal barrier function, immune parameters, and the expression of intestinal development-related genes in weaning pigs. One hundred and forty-four 25-d-old weaning piglets with BW of 6.43 ± 0.39 kg were randomly allotted to 1 of 4 dietary treatments: 1) CON (basal diet; control), 2) SDPP (containing 5% SDPP), 3) SDPP + SDCP (containing 2...
January 2016: Journal of Animal Science
Bongki Kim, Sylvie Breton
The initial segment (IS) in rodents is functionally and structurally distinct from other epididymal segments and plays an important role in sperm maturation. The MAPK/ERK1/2 pathway is maintained active in the IS by testicular luminal factors and plays crucial roles in the maintenance and differentiation of the IS epithelium. Tight junctions (TJs) are constituents of the blood-epididymis barrier, which mediates the paracellular transport of ions, solutes, and water and controls epithelial cell differentiation, thereby contributing to the establishment of a unique luminal environment...
January 2016: Biology of Reproduction
Boris D Jaimes-Parra, Francisco Valle-Díaz de la Guardia, Miguel Á Arrabal-Polo, Bernardo Herrera-Imbroda, María F Lara, Francisco-Javier Machuca-Santa-Cruz, Antonio Campos, Miguel Alaminos, Pascual V Crespo, Ingrid Garzón
OBJECTIVE: To generate and to evaluate ex vivo a novel model of bioengineered human bladder mucosa based on fibrin-agarose biomaterials. METHODS: We first established primary cultures of stromal and epithelial cells from small biopsies of the human bladder using enzymatic digestion and selective cell culture media. Then, a bioengineered substitute of the bladder lamina propria was generated using cultured stromal cells and fibrin-agarose scaffolds, and the epithelial cells were then subcultured on top to generate a complete bladder mucosa substitute...
January 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
Melissa Sambrotta, Richard J Thompson
Progressive familial intrahepatic cholestasis is a clinical description of a phenotype, which we now realize has several different genetic aetiologies. The identification of the underlying genetic defects has helped to elucidate important aspects of liver physiology. The latest addition to this family of diseases is tight junction protein 2 (TJP2) deficiency. This protein is also known as zona occludens 2 (ZO-2). The patients, so far presented, all have homozygous, protein-truncating mutations. A complete absence of this protein was demonstrated...
July 2015: Tissue Barriers
G B Sadowska, N Ahmedli, X Chen, B S Stonestreet
Tight junctions of the blood-brain barrier are composed of transmembrane and associated cytoplasmic proteins. The transmembrane claudin proteins form the primary seal between endothelial cells and junctional adhesion molecules (JAMs) regulate tight junction formation. We have previously shown that claudin-1, claudin-5, zonula occludens (ZO)-1, and ZO-2 exhibit differential developmental regulation from 60% of gestation up to maturity in adult sheep. The purpose of the current study was to examine developmental changes in claudin-3, -12, and JAM-A protein expression in cerebral cortices of fetuses at 60%, 80%, and 90% gestation, and in newborn and adult sheep...
December 3, 2015: Neuroscience
Ning Jiao, Zhenlong Wu, Yun Ji, Bin Wang, Zhaolai Dai, Guoyao Wu
BACKGROUND: L-Glutamate (Glu) is a major amino acid in milk and postweaning diets for mammals (including pigs and human infants). However, effects of Glu on intestinal mucosal barrier and antioxidative functions are unknown. OBJECTIVE: This study tested the hypothesis that Glu may enhance the barrier function of intestinal porcine epithelial cell line 1 (IPEC-1) cells by upregulating the expression of tight junction proteins. METHODS: IPEC-1 cells were cultured with or without Glu in the presence or absence of 1 mmol/L diquat (an oxidant) for indicated time points...
October 2015: Journal of Nutrition
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