scholarly journals Necrotizing enterocolitis intestinal barrier function protection by antenatal dexamethasone and surfactant-D in a rat model

2021 ◽  
Author(s):  
Lei Lu ◽  
Jing Lu ◽  
Yueyue Yu ◽  
Erika Claud
Keyword(s):  
Tight Junction ◽  
Platelet Activating Factor ◽  
Intestinal Barrier ◽  
Surfactant Protein ◽  
Mucosal Barrier ◽  
Surfactant Protein D ◽  
Barrier Integrity ◽  
Junction Protein ◽  
Junction Proteins

Abstract Background Necrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature neonates. Possible therapeutic approaches are centered on promoting maturation of the gastrointestinal mucosal barrier. Studies have demonstrated that antenatal administration of corticosteroids can decrease NEC incidence and mortality. Methods Pregnant rat dams were administered dexamethasone 48 h prior to delivery. The pups were subjected to an experimental NEC-like injury protocol. Ileal tissues and sera were collected and evaluated for inflammatory cytokines, gut permeability and expressions and localizations of tight junction proteins, and surfactant protein-D by immunohistochemistry/immunofluorescent staining. Intestinal epithelial cells (IEC-6) were pretreated with SP-D to examine the effect of SP-D on tight junction protein expressions when challenged with platelet-activating factor and lipopolysaccharide to model proinflammatory insults. Results Antenatal dexamethasone reduced systemic inflammation, preserved intestinal barrier integrity, and stimulated SP-D expression on the intestinal mucosal surface in pups exposed to NEC-like injury. Pretreatment of SP-D blocked platelet-activating factor/lipopolysaccharide-induced tight junction disruption in IEC-6 cells in vitro. Conclusions Antenatal dexamethasone preserves the development of intestinal mucosal barrier integrity and reduces incidence and morbidity from an experimental NEC-like injury model. Dexamethasone upregulation of intestinal SP-D-protective effects on tight junction proteins. Impact Antenatal administration of dexamethasone can function in concert with intestinal surfactant protein-D to decrease systemic inflammatory responses, and protect intestinal barrier integrity in a neonatal rat model of NEC. A novel role of intestinal SP-D in preserving tight junction protein structures under inflammatory conditions. We describe the intestinal SP-D—an overlooked role of antenatal dexamethasone in neonatal NEC?

Protection of Intestinal Barrier in Uremic Mice by Electroacupuncture via Regulating the Cannabinoid 1 Receptor of the Intestinal Glial Cells

2021 ◽  
Vol 17 (11) ◽  
pp. 2210-2218
Author(s):  
Feng Li ◽  
Guangjian Zhang ◽  
Jing Liang ◽  
Yu Ma ◽  
Jian Huang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Glial Cells ◽  
Cannabinoid Receptor ◽  
Intestinal Barrier ◽  
Mice Model ◽  
Jnk Pathway ◽  
Cannabinoid 1 Receptor ◽  
Junction Protein ◽  
Receptor Signaling Pathway ◽  
Junction Proteins

Intestinal barrier injuries are common in uremia, which aggravates uremia. The goal of this study is to learn moreabout how electroacupuncture regulates gastrointestinal function, as well as to identify the importance of microglia in electroacupuncture regulation and the cannabinoid receptor signaling pathway in controlling the activity of intestinal glial cells. The mice were arbitrarily assigned to four groups: control, CKD, electroacupuncture stimulation, or AM251 (CB1 receptor antagonist). The mice model of uremia was established by adenine gavage. Western blotting revealed the development of tight junction proteins ZO-1, cannabinoid 1 receptor, glial specific GFAP, occludin, S100 β, claudin-1, and JNK. GFAP and CB1R protein expression and co-localization of the intestinal glial cells were observed by double-labeled fluorescence. The expression of cannabinoid 1 receptor CB1R in the intestinal glial cells was increased after electroacupuncture. The expression of tight junction protein, GFAP, S100 β, and CB1R protein was up-regulated after electroacupuncture, and the dysfunction of the intestinal barrier in uremia was corrected. Nevertheless, AM251, a CB1R antagonist, reversed the effect of electroacupuncture. Electroacupuncture can protect the intestinal barrier through the intestinal glial cell CB1R, and the effect is achieved by inhibiting the JNK pathway.

scholarly journals The Tight Junction Proteins Claudin-1, -6, and -9 Are Entry Cofactors for Hepatitis C Virus

2008 ◽  
Vol 82 (7) ◽  
pp. 3555-3560 ◽  
Author(s):  
Laurent Meertens ◽  
Claire Bertaux ◽  
Lisa Cukierman ◽  
Emmanuel Cormier ◽  
Dimitri Lavillette ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Tight Junction ◽  
Tight Junction Proteins ◽  
Junction Protein ◽  
Cellular Factors ◽  
Cd81 Tetraspanin ◽  
Junction Proteins

ABSTRACT Hepatitis C virus (HCV) is a major cause of liver disease in humans. The CD81 tetraspanin is necessary but not sufficient for HCV penetration into hepatocytes, and it was recently reported that the tight junction protein claudin-1 is a critical HCV entry cofactor. Here, we confirm the role of claudin-1 in HCV entry. In addition, we show that claudin-6 and claudin-9 expressed in CD81+ cells also enable the entry of HCV pseudoparticles derived from six of the major genotypes. Whereas claudin-1, -6, and -9 function equally well as entry cofactors in endothelial cells, claudin-1 is more efficient in hepatoma cells. This suggests that additional cellular factors modulate the ability of claudins to function as HCV entry cofactors. Our work has generated novel and essential means to investigate the mechanism of HCV penetration into hepatocytes and the role of the claudin protein family in HCV dissemination, replication, and pathogenesis.

scholarly journals Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function

2019 ◽  
Author(s):  
Jingtao Wu ◽  
Caimei He ◽  
Jie Bu ◽  
Yue Luo ◽  
Shuyuan Yang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Inflammatory Factors ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Junction Protein ◽  
Epithelial Barriers ◽  
Junction Proteins

Abstract Background: The intestinal epithelial barrier, which works as the first line of defense between the intestinal environment and the parasitifer, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine (Bet) has excellent anti-inflammatory activity but whether Bet has any effect on tight junction proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model, the purpose of this study is to explore the pharmacological effect of Bet on improving intestinal barrier function represented by TJ proteins.Results: The results demonstrated that Bet enhanced the expression of tight junction proteins while LPS（ 1μg /m L）downregulates the expression of these proteins. Furthermore, Bet attenuates LPS-induced decreases of tight junction proteins both shown by WB and RT-PCR. The immunofluorescent images consistently revealed that LPS induced the disruption of tight junction protein Claudin-1 and reduced its expression while Bet could reverse these alterations. Similar protective role of Bet on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach. Conclusion: In conclusion, our research demonstrated that Bet attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.

scholarly journals Effects of Methylmethionine Sulfonium Chloride on Activity and Tight Junction Protein Expression of Intestinal Porcine Jejunum Epithelial Cells (IPEC-J2)

2021 ◽  
Author(s):  
Jianping Yang ◽  
Xinfeng Li ◽  
Xinlei Wang ◽  
Xin Wen ◽  
Tongtong Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Tight Junction ◽  
Barrier Function ◽  
Quantitative Polymerase Chain Reaction ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Epithelial Cell Line ◽  
Tight Junction Proteins ◽  
Junction Protein ◽  
Junction Proteins

Background: The intestinal mucosal epithelium acts as a physical and biochemical barrier and plays an important role in regulating of barrier function and immune homeostasis. Methylmethionine sulfonium chloride (MMSC) is a multifaceted amino acid that is critical to the normal physiology of the gastrointestinal tract. The present study investigated the effects of extracellular MMSC on intestinal epithelial cell line (IPEC-J2). Methods: IPEC-J2 cells were treated with 0.1, 0.5 and 1 mM MMSC, respectively for an additional 24 h. CCK-8 assay was used to evaluate cell proliferation. The cell Annexin V-FITC/PI apoptosis were analyzed by flow cytometry (FCM) method. The mRNA transcript and protein expression levels of tight junction proteins in IPEC-J2 cells were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB). Result: The results showed that MMSC could stimulate IPEC-J2 cells proliferation and inhibit cell apoptosis. In addition, the RT-qPCR and WB results indicated that 0.5 mM MMSC significantly increased the mRNA and protein expression of tight junction proteins, including occludin, claudin-1 and zonula occludin-1 (Zo-1). These findings may provide valuable information to investigate further the possible mechanism and function of MMCS on the intestinal barrier function.

The role of surfactant protein D in fibrotic lung remodelling

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
J Viereck ◽  
L Knudsen ◽  
JP Schneider ◽  
M Ochs ◽  
T Thum
Keyword(s):  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Lung Remodelling

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

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