A new role for reticulon-4B/NOGO-B in the intestinal epithelial barrier function and inflammatory bowel disease

2015 ◽  
Vol 308 (12) ◽  
pp. G981-G993 ◽  
Author(s):  
Juan Antonio Rodríguez-Feo ◽  
Marta Puerto ◽  
Carolina Fernández-Mena ◽  
Cristina Verdejo ◽  
José Manuel Lara ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Inflammatory Bowel ◽  
E Cadherin

Inflammatory bowel disease (IBD) is characterized by an impaired intestinal barrier function. We aimed to investigate the role of reticulon-4B (RTN-4B/NOGO-B), a structural protein of the endoplasmic reticulum, in intestinal barrier function and IBD. We used immunohistochemistry, confocal microscopy, real-time PCR, and Western blotting to study tissue distribution and expression levels of RTN-4B/NOGO-B in control and IBD samples from mouse and humans. We also targeted RTN-4B/NOGO-B using siRNAs in cultured human intestinal epithelial cell (IECs). Epithelial barrier permeability was assessed by transepithelial electrical resistance (TEER) measurement. RTN-4B/NOGO-B is expressed in the intestine mainly by IECs. Confocal microscopy revealed a colocalization of RTN-4B, E-cadherin, and polymerized actin fibers in tissue and cultured IECs. RTN-4B mRNA and protein expression were lower in the colon of IL-10−/− compared with wild-type mice. Colocalization of RTN-4B/E-cadherin/actin was reduced in the colon of IL-10−/− mice. Analysis of endoscopic biopsies from IBD patients showed a significant reduction of RTN-4B/NOGO-B expression in inflamed mucosa compared with control. Treatment of IECs with H2O2 reduced TEER values and triggered phosphorylation of RTN-4B in serine 107 residues as well as downregulation of RTN-4B expression. Acute RTN-4B/NOGO-B knockdown by siRNAs resulted in a decreased TEER values and reduction of E-cadherin and α-catenin expression and in the amount of F-actin-rich filaments in IECs. Epithelial RTN-4B/NOGO-B was downregulated in human and experimental IBD. RTN-4B participates in the intestinal epithelial barrier function, most likely via its involvement in E-cadherin, α-catenin expression, and actin cytoskeleton organization at sites of cell-to-cell contacts.

scholarly journals Plumericin Protects against Experimental Inflammatory Bowel Disease by Restoring Intestinal Barrier Function and Reducing Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  
Keyword(s):  
Barrier Function ◽  
Structural Integrity ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.

Dietary fibre-based SCFA mixtures promote both protection and repair of intestinal epithelial barrier function in a Caco-2 cell model

2017 ◽  
Vol 8 (3) ◽  
pp. 1166-1173 ◽  
Author(s):  
Tingting Chen ◽  
Choon Young Kim ◽  
Amandeep Kaur ◽  
Lisa Lamothe ◽  
Maliha Shaikh ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Barrier Function ◽  
Cell Model ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Gut Barrier Function ◽  
Inflammatory Bowel

Impaired gut barrier function plays an important role in the development of many diseases such as obesity, inflammatory bowel disease, and in HIV infection.

Vitamin A inhibits the action of LPS on the intestinal epithelial barrier function and tight junction proteins

2019 ◽  
Vol 10 (2) ◽  
pp. 1235-1242 ◽  
Author(s):  
Caimei He ◽  
Jun Deng ◽  
Xin Hu ◽  
Sichun Zhou ◽  
Jingtao Wu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Intestinal Barrier ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
Inflammatory Bowel ◽  
Junction Proteins

Inflammation caused by either intrinsic or extrinsic toxins results in intestinal barrier dysfunction, contributing to inflammatory bowel disease (IBD) and other diseases.

scholarly journals 3343 Identification of host-microbial interaction networks that mediate intestinal epithelial barrier function in necrotizing enterocolitis

2019 ◽  
Vol 3 (s1) ◽  
pp. 13-13
Author(s):  
David R Hill ◽  
Roberto Cieza ◽  
Veda K. Yadagiri ◽  
Phillip Tarr ◽  
Jason R. Spence ◽  
...  
Keyword(s):  
Barrier Function ◽  
Bacterial Colonization ◽  
Intestinal Barrier ◽  
Microbial Interactions ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Epithelial Barrier Function ◽  
Novel Approach ◽  
Species Specific

OBJECTIVES/SPECIFIC AIMS: The central goal of this proposal is to characterize the mechanisms that mediate success or failure of immature intestinal barrier in necrotizing enterocilitis. METHODS/STUDY POPULATION: To do this, I will utilize stem cell derived human intestinal organoids (HIOs), an innovative model of the immature intestine, and a cohort of bacterial isolates collected from premature infants who developed NEC to interrogate the cause-effect relationship of these strains on maintenance of the intestinal barrier. I hypothesize that the epithelial response to bacterial colonization is strain-dependent and results in differences in inflammatory signaling that shape epithelial barrier function in the immature intestine. RESULTS/ANTICIPATED RESULTS: Preliminary data shows that colonization of HIOs with different bacteria leads to species-specific changes in barrier function, and some species selectively damage the epithelial barrier while others enhance epithelial barrier function. I have identified key inflammatory signals that serve as central drivers of intestinal barrier function. DISCUSSION/SIGNIFICANCE OF IMPACT: Characterization of this process is expected to substantially advance scientific understanding of early events in NEC pathogenesis and lead to new opportunities for targeted therapeutic intervention to accelerate barrier maturation or prevent hyperinflammatory reactivity in the neonatal intestine. The research proposed in this application represents an entirely novel approach to studying host-microbial interactions in the immature. Conceptually, this novel translational approach will help to define the pivotal role of colonizing bacteria in initiating epithelial inflammation in NEC patients.

P150 ENHANCING EPITHELIAL BARRIER FUNCTION WITH NOVEL E-CADHERIN ACTIVATING MONOCLONAL ANTIBODIES REDUCES INFLAMMATORY BOWEL DISEASE PROGRESSION IN MOUSE MODELS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S29-S30
Author(s):  
Chirosree Bandyopadhyay ◽  
Leslayann Schecterson ◽  
Barry Gumbiner
Keyword(s):  
Inflammatory Bowel Disease ◽  
Monoclonal Antibodies ◽  
Treatment Group ◽  
Mouse Models ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Transfer Model ◽  
Epithelial Barrier Function ◽  
Inflammatory Bowel ◽  
E Cadherin

Abstract Deficits in gastrointestinal (GI) epithelial barrier function play important roles in the pathogenesis of Inflammatory Bowel Disease (IBD). The CDH1 gene encoding E-cadherin, a key component of the epithelial junctional complex, is associated with Ulcerative Colitis (UC), and perhaps Crohn’s disease (CD). E-cadherin is the principle adhesive component of the adherens junction, and it regulates paracellular permeability by facilitating the formation of tight junctions and organizing the entire epithelial junction complex. We have identified monoclonal antibodies (mAbs) that bind to E-cadherin and activate adhesion in a variety of epithelial cells. In this study, we aim to test the hypothesis that strengthening E-cadherin adhesion with activating mAbs will enhance barrier function and decrease progression of IBD while maintaining mucosal health and homeostasis. Mouse mAbs to E-cadherin have been tested in vivo using the IL10-knock out mouse and adoptive T cell transfer model of colitis with similar histological evaluation. Transfer of CD4+CD45Rb high T cells from donor to immunocompromised mice produced typical histologic lesions for the adoptive transfer model including inflammation of the mucosa/submucosa, crypt damage, erosions, edema, and epithelial hyperplasia. E-Cadherin activating mAb (r56.4) treatment reduced total colitis score, mucosal hyperplasia, inflammation, gland loss scores, and neutrophilic infiltration in CD45Rb high T cell recipient mice compared to control E-cad mAb (r19.1–10) treatment. In IL10 KO BL6 mouse model of colitis, average lesion severity scores were lower in the r56.4 treatment group in comparison to the r19.1–10 treatment group for all the histological hallmarks of colitis. Further studies are in progress to investigate the therapeutic potential of E-Cadherin mAbs in the rescue of inflammation in pre-clinical mouse models of colitis.

scholarly journals H19Long Noncoding RNA Regulates Intestinal Epithelial Barrier Function via MicroRNA 675 by Interacting with RNA-Binding Protein HuR

2016 ◽  
Vol 36 (9) ◽  
pp. 1332-1341 ◽  
Author(s):  
Tongtong Zou ◽  
Suraj K. Jaladanki ◽  
Lan Liu ◽  
Lan Xiao ◽  
Hee Kyoung Chung ◽  
...  
Keyword(s):  
Barrier Function ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
E Cadherin

The disruption of the intestinal epithelial barrier function occurs commonly in various pathologies, but the exact mechanisms responsible are unclear. TheH19long noncoding RNA (lncRNA) regulates the expression of different genes and has been implicated in human genetic disorders and cancer. Here, we report thatH19plays an important role in controlling the intestinal epithelial barrier function by serving as a precursor for microRNA 675 (miR-675).H19overexpression increased the cellular abundance of miR-675, which in turn destabilized and repressed the translation of mRNAs encoding tight junction protein ZO-1 and adherens junction E-cadherin, resulting in the dysfunction of the epithelial barrier. Increasing the level of the RNA-binding protein HuR in cells overexpressingH19prevented the stimulation of miR-675 processing fromH19, promoted ZO-1 and E-cadherin expression, and restored the epithelial barrier function to a nearly normal level. In contrast, the targeted deletion of HuR in intestinal epithelial cells enhanced miR-675 production in the mucosa and delayed the recovery of the gut barrier function after exposure to mesenteric ischemia/reperfusion. These results indicate thatH19interacts with HuR and regulates the intestinal epithelial barrier function via theH19-encoded miR-675 by altering ZO-1 and E-cadherin expression posttranscriptionally.

Collagen peptides ameliorate intestinal epithelial barrier dysfunction in immunostimulatory Caco-2 cell monolayers via enhancing tight junctions

2017 ◽  
Vol 8 (3) ◽  
pp. 1144-1151 ◽  
Author(s):  
Qianru Chen ◽  
Oliver Chen ◽  
Isabela M. Martins ◽  
Hu Hou ◽  
Xue Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Intestinal Epithelial Barrier ◽  
Cell Monolayers ◽  
Collagen Peptides ◽  
Epithelial Barrier Dysfunction

Alaska pollock skin derived collagen peptides could be considered as dietary supplements for intestinal barrier function promotion and associated diseases.

scholarly journals Succinate Modulates Intestinal Barrier Function and Inflammation Response in Pigs

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 486 ◽  
Author(s):  
Li ◽  
Mao ◽  
Zhang ◽  
Yu ◽  
Zhu
Keyword(s):  
Barrier Function ◽  
Growing Pigs ◽  
Intestinal Morphology ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Control Group ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function

Succinate is a metabolic intermediate of the tricarboxylic acid (TCA) cycle in all aerobic organisms, and is also a vital microbial metabolite in the gut. Although succinate is known to regulate intestinal metabolism and immune function, its role in the protection of the intestinal epithelial barrier function and inflammation is poorly characterized. In this study, we evaluated the effects of succinate on intestinal epithelial barrier function and inflammation in pigs. Twenty-four growing pigs were distributed into three groups (n = 8) and received either a basal diet (control group) or the same diet supplemented with 0.1% succinate or 1% succinate. The diet supplemented with 1% succinate led to alterations in the intestinal morphology. We confirmed in vitro that 5 mM succinate treatment modulated intestinal epithelial permeability by increased transepithelial electrical resistance (TEER) in intestinal porcine epithelial cell (IPEC)-J2 cells. Furthermore, succinate treatment increased the abundance of tight junction proteins claudin-1, zona occluden (ZO)-1, and ZO-2 in the jejunum in vivo and in vitro. In addition, dietary succinate supplementation promoted the expression of inflammatory cytokines interleukin (IL)-25, IL-10, IL-8, and IL-18 in the jejunum. Taken together, these data identify a novel role of succinate in the modulation of intestinal epithelial barrier function, which may be a nutritional target to improve gut health in animals.

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