Damage to intestinal barrier integrity in piglets caused by porcine reproductive and respiratory syndrome virus infection

AbstractPorcine reproductive and respiratory syndrome (PRRS) induces respiratory disease and reproductive failure accompanied by gastroenteritis-like symptoms. The mechanism of intestinal barrier injury caused by PRRSV infection in piglets has yet to be investigated. An in vivo PRRSV-induced model was established in 30-day-old piglets by the intramuscular injection of 2 mL of 104 TCID50/mL PRRSV for 15 days. Observations of PRRSV replication and histology were conducted in the lungs and intestine, and goblet cell counts, relative MUC2 mRNA expression, and tight junction protein, proinflammatory cytokine, TLR4, MyD88, IκB and p-IκB expression were measured. PRRSV replicated in the lungs and small intestine, as demonstrated by absolute RT-qPCR quantification, and the PRRSV N protein was detected in the lung interstitium and jejunal mucosa. PRRSV infection induced both lung and gut injury, markedly decreased villus height and the villus to crypt ratio in the small intestine, and obviously increased the number of goblet cells and the relative expression of MUC2 mRNA in the jejunum. PRRSV infection aggravated the morphological depletion of tight junction proteins and increased IL-1β, IL-6, IL-8 and TNF-α expression by activating the NF-κB signalling pathway in the jejunum. PRRSV infection impaired intestinal integrity by damaging physical and immune barriers in the intestine by inducing inflammation, which may be related to the regulation of the gut-lung axis. This study also provides a new hypothesis regarding the pathogenesis of PRRSV-induced diarrhoea.

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Antiviral effects of ergosterol peroxide in a pig model of porcine deltacoronavirus (PDCoV) infection involves modulation of apoptosis and tight junction in the small intestine

Veterinary Research ◽

10.1186/s13567-021-00955-5 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Cong Duan ◽

Junchi Wang ◽

Yi Liu ◽

Jialu Zhang ◽

Jianyong Si ◽

...

Keyword(s):

Small Intestine ◽

Tight Junction ◽

In Vitro Study ◽

Mapk Signaling ◽

Intestinal Lesion ◽

Ergosterol Peroxide ◽

Junction Protein ◽

Induced Apoptosis

AbstractPorcine deltacoronavirus (PDCoV) is a newly discovered swine enteropathogenic coronavirus with worldwide distribution. However, efficient strategies to prevent or treat the infection remain elusive. Our in vitro study revealed that ergosterol peroxide (EP) from the mushroom Cryptoporus volvatus has efficient anti-PDCoV properties. The aim of this study is to evaluate the potential of EP as a treatment for PDCoV in vivo and elucidate the possible mechanisms. Seven-day-old piglets were infected with PDCoV by oral administration in the presence or absence of EP. Piglets infected with PDCoV were most affected, whereas administration of EP reduced diarrhea incidence, alleviated intestinal lesion, and decreased viral load in feces and tissues. EP reduced PDCoV-induced apoptosis and enhanced tight junction protein expressions in the small intestine, maintaining the integrity of the intestinal barrier. EP showed immunomodulatory effect by suppressing PDCoV-induced pro-inflammatory cytokines and the activation of IκBα and NF-κB p65, and upregulating IFN-I expression. Knockdown of p38 inhibited PDCoV replication and alleviated PDCoV-induced apoptosis, implying that EP inhibited PDCoV replication and alleviated PDCoV-induced apoptosis via p38/MAPK signaling pathway. Collectively, ergosterol peroxide can protect piglets from PDCoV, revealing the potential of EP for development as a promising strategy for treating and controlling the infection of PDCoV.

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Spermine Protects Intestinal Barrier Integrity Through Rac1/PLC-γ1 Signalling Pathway in Piglets

10.21203/rs.3.rs-102466/v1 ◽

2020 ◽

Author(s):

Guangmang Liu ◽

Xiaomei Xu ◽

Caimei Wu ◽

Gang Jia ◽

Hua Zhao ◽

...

Keyword(s):

Tight Junction ◽

Intestinal Barrier ◽

Signalling Pathway ◽

Tight Junction Protein ◽

Intestinal Integrity ◽

Tnf Α ◽

Junction Protein ◽

Intestinal Barrier Integrity

Abstract Background: Weaning stress can lead to the disruption of tight junctions and increased intestinal permeabilty, which contributes to the initiation and development of many disease, such as Crohn’s disease and ulcerative colitis. Pigs are more ideal models for human studies than other animals. However, no information is found about the relationship of intestinal integrity and spermine supplementation in pigs. The objective of this study is to investigate whether spermine protects intestinal barrier integrity via Rac1/PLC-γ1 signalling pathway in piglets. Methods: In vivo, the piglets were categorised into the control group and the spermine group, which was fed with spermine at 0.4 mmol kg−1 body weight for 7 hours and 3, 6 and 9 days. In vitro, we examined whether spermine protects the intestinal barrier after TNF-α challenge through Ras-related C3 botulinum toxin substrate 1 (Rac1)/Phospho-lipase C-γ1 (PLC-γ1) signalling pathway. Results: In vivo study revealed that the spermine treatment upregulated tight junction protein mRNA levels and Rac1/PLC-γ1 signalling pathway gene expression in the jejunum of piglets. The serum D-lactate content was significantly reduced after spermine treatment (P < 0.05). In vitro study revealed that 0.1 μM spermine significantly increased the levels of tight junction protein expression, Rac1/PLC-γ1 signalling pathway and transepithelial electrical resistance, and decreased paracellular permeability (P < 0.05). Further experiments showed that spermine treatment increased the levels of tight junction protein expression, Rac1/PLC-γ1 signalling pathway and transepithelial electrical resistance, and decreased paracellular permeability compared with the NSC-23766 and U73122 treatment with spermine after TNF-α challenge (P < 0.05). Conclusion: spermine protects intestinal integrity through the Rac1/PLC-γ1 signalling pathway.

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Changes in tight junction protein expression in intrinsic aging and photoaging in human skin in vivo

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2016.07.002 ◽

2016 ◽

Vol 84 (1) ◽

pp. 99-101 ◽

Cited By ~ 10

Author(s):

Seon-Pil Jin ◽

Sang Bum Han ◽

Yeon Kyung Kim ◽

Elizabeth Eunkyung Park ◽

Eun Jin Doh ◽

...

Keyword(s):

Protein Expression ◽

Tight Junction ◽

Human Skin ◽

Tight Junction Protein ◽

Tight Junction Protein Expression ◽

Junction Protein

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Hyaluronan 35 kDa treatment protects mice from Citrobacter rodentium infection and induces epithelial tight junction protein ZO-1 in vivo

Matrix Biology ◽

10.1016/j.matbio.2016.11.001 ◽

2017 ◽

Vol 62 ◽

pp. 28-39 ◽

Cited By ~ 11

Author(s):

Yeojung Kim ◽

Sean P. Kessler ◽

Dana R. Obery ◽

Craig R. Homer ◽

Christine McDonald ◽

...

Keyword(s):

Tight Junction ◽

Tight Junction Protein ◽

Citrobacter Rodentium ◽

Junction Protein ◽

Epithelial Tight Junction

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

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3186 ◽

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.

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Decreased tight junction protein intensity in the placenta of porcine reproductive and respiratory syndrome virus-2 infected fetuses

Placenta ◽

10.1016/j.placenta.2021.07.300 ◽

2021 ◽

Author(s):

Pauline B. Guidoni ◽

Jonathan A. Pasternak ◽

Glenn Hamonic ◽

Daniel J. MacPhee ◽

John C.S. Harding

Keyword(s):

Tight Junction ◽

Tight Junction Protein ◽

Respiratory Syndrome Virus ◽

Junction Protein

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Regulation of testicular tight junctions by gonadotrophins in the adult Djungarian hamster in vivo

Reproduction ◽

10.1530/rep-07-0572 ◽

2008 ◽

Vol 135 (6) ◽

pp. 867-877 ◽

Cited By ~ 38

Author(s):

Gerard A Tarulli ◽

Sarah J Meachem ◽

Stefan Schlatt ◽

Peter G Stanton

Keyword(s):

Tight Junction ◽

Adaptor Protein ◽

Tight Junction Protein ◽

Mrna Levels ◽

Tight Junction Proteins ◽

Djungarian Hamster ◽

Junction Protein ◽

Protein Localisation ◽

Junction Proteins

This study aimed to assess the effect of gonadotrophin suppression and FSH replacement on testicular tight junction dynamics and blood–testis barrier (BTB) organisation in vivo, utilising the seasonal breeding Djungarian hamster. Confocal immunohistology was used to assess the cellular organisation of tight junction proteins and real-time PCR to quantify tight junction mRNA. The effect of tight junction protein organisation on the BTB permeability was also investigated using a biotin-linked tracer. Tight junction protein (claudin-3, junctional adhesion molecule (JAM)-A and occludin) localisation was present but disorganised after gonadotrophin suppression, while mRNA levels (claudin-11, claudin-3 and occludin) were significantly (two- to threefold) increased. By contrast, both protein localisation and mRNA levels for the adaptor protein zona occludens-1 decreased after gonadotrophin suppression. FSH replacement induced a rapid reorganisation of tight junction protein localisation. The functionality of the BTB (as inferred by biotin tracer permeation) was found to be strongly associated with the organisation and localisation of claudin-11. Surprisingly, JAM-A was also recognised on spermatogonia, suggesting an additional novel role for this protein in trans-epithelial migration of germ cells across the BTB. It is concluded that gonadotrophin regulation of tight junction proteins forming the BTB occurs primarily at the level of protein organisation and not gene transcription in this species, and that immunolocalisation of the organised tight junction protein claudin-11 correlates with BTB functionality.

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Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00327.2009 ◽

2010 ◽

Vol 298 (6) ◽

pp. G851-G859 ◽

Cited By ~ 288

Author(s):

Jurgen Karczewski ◽

Freddy J. Troost ◽

Irene Konings ◽

Jan Dekker ◽

Michiel Kleerebezem ◽

...

Keyword(s):

Tight Junction ◽

Lactobacillus Plantarum ◽

Transmembrane Protein ◽

Intestinal Barrier ◽

Protective Effects ◽

Epithelial Tight Junction ◽

Vitro Model ◽

Probiotic Mechanisms

Lactobacillus plantarum , a commensal bacterium of humans, has been proposed to enhance the intestinal barrier, which is compromised in a number of intestinal disorders. To study the effect of L. plantarum strain WCFS1 on human barrier function, healthy subjects were administered L. plantarum or placebo in the duodenum for 6 h by means of a feeding catheter. The scaffold protein zonula occludens (ZO)-1 and transmembrane protein occludin were found to be significantly increased in the vicinity of the tight-junction (TJ) structures, which form the paracellular seal between cells of the epithelium. In an in vitro model of the human epithelium, L. plantarum induced translocation of ZO-1 to the TJ region; however, the effects on occludin were minor compared with those seen in vivo. L. plantarum was shown to activate Toll-like receptor 2 (TLR2) signaling, and treatment of Caco-2 monolayers with the TLR2 agonist Pam3-Cys-SK4(PCSK) significantly increased fluorescent staining of occludin in the TJ. Pretreatment of Caco-2 monolayers with L. plantarum or PCSK significantly attenuated the effects of phorbol ester-induced dislocation of ZO-1 and occludin and the associated increase in epithelial permeability. Our results identifying commensal bacterial stimulation of TLR2 in the gut epithelium as a regulator of epithelial integrity have important implications for understanding probiotic mechanisms and the control of intestinal homeostasis.

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