scholarly journals Effect of Perfluorooctanoic Acid on the Epigenetic and Tight Junction Genes of the Mouse Intestine

Toxics ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 64 ◽  
Author(s):  
Faizan Rashid ◽  
Saeed Ahmad ◽  
Joseph Maria Kumar Irudayaraj
Keyword(s):  
Small Intestine ◽  
Tight Junction ◽  
Reproductive Toxicity ◽  
Perfluorooctanoic Acid ◽  
Dna Methyltransferases ◽  
Expression Of Genes ◽  
Junction Protein ◽  
Mouse Intestine ◽  
Cd1 Mice ◽  
High Concentrations

Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, genotoxicity, nephrotoxicity, epigenetic toxicity, immunotoxicity, reproductive toxicity, and hepatotoxicity. However, information on the accumulation of PFOA in the intestine and its toxic effects on intestinal epigenetics and tight junction (TJ) genes is sparse. CD1 mice were dosed with PFOA (1, 5, 10, or 20 mg/kg/day) for 10 days, and its accumulation and induced alterations in the expression of epigenetic and tight junction genes in the small intestine and colon were evaluated using LC–MS and qPCR techniques. PFOA reduced the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b) primarily in the small intestine whereas, in the colon, a decrease was observed only at high concentrations. Moreover, ten-eleven translocation genes (Tet2 and Tet3) expression was dysregulated in the small intestine, whereas in the colon Tets remained unaffected. The tight junction genes Claudins (Cldn), Occludin (Ocln), and Tight Junction Protein (Tjp) were also heavily altered in the small intestine. TJs responded differently across the gut, in proportion to PFOA dosing. Our study reveals that PFOA triggers DNA methylation changes and alters the expression of genes essential for maintaining the physical barrier of intestine, with more profound effects in the small intestine compared to the colon.

scholarly journals Conjugal Transfer of the Salmonella enterica Virulence Plasmid in the Mouse Intestine

2008 ◽  
Vol 190 (6) ◽  
pp. 1922-1927 ◽  
Author(s):  
Meritxell García-Quintanilla ◽  
Francisco Ramos-Morales ◽  
Josep Casadesús
Keyword(s):  
Small Intestine ◽  
Salmonella Enterica ◽  
Sodium Deoxycholate ◽  
Distal Portion ◽  
Conjugal Transfer ◽  
Virulence Plasmid ◽  
Low Frequencies ◽  
Serovar Typhimurium ◽  
Mouse Intestine ◽  
High Concentrations

ABSTRACT BALB/c mice were infected with two Salmonella enterica serovar Typhimurium strains, one of which lacked the virulence plasmid. Transconjugants were found at high frequencies in the mouse feces and at low frequencies in the liver and the spleen, suggesting that mating occurred in the gut. Laboratory conditions that mimic those of the small intestine (microaerophilic growth in the presence of 0.3 M NaCl) increased the frequency of virulence plasmid transfer. Sodium deoxycholate, which is found at high concentrations in the duodenum, and sodium propionate, which is abundant in the large intestine, reduced the conjugation frequency. Feces inhibited conjugation. Altogether, these observations suggested that transfer of the virulence plasmid occurred in the distal portion of the small intestine. Conjugation trials in ileal loops provided direct evidence that conjugal transfer of the Salmonella virulence plasmid occurs in the ileum in mice.

scholarly journals Changes of Tight Junction Protein Claudins in Small Intestine and Kidney Tissues of Mice Fed a DDC Diet

2013 ◽  
Vol 26 (4) ◽  
pp. 433-438 ◽  
Author(s):  
Yukie Abiko ◽  
Takashi Kojima ◽  
Masaki Murata ◽  
Mitsuhiro Tsujiwaki ◽  
Masaya Takeuchi ◽  
...  
Keyword(s):  
Small Intestine ◽  
Tight Junction ◽  
Tight Junction Protein ◽  
Junction Protein

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

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Jin Zhao ◽  
Shuangxiu Wan ◽  
Na Sun ◽  
Panpan Sun ◽  
Yaogui Sun ◽  
...  
Keyword(s):  
Small Intestine ◽  
Tight Junction ◽  
Intestinal Barrier ◽  
Respiratory Syndrome Virus ◽  
Jejunal Mucosa ◽  
N Protein ◽  
Cell Counts ◽  
Junction Protein ◽  
Qpcr Quantification

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.

scholarly journals Endocytosis takes occludin for a ride

2010 ◽  
Vol 189 (1) ◽  
pp. 7-7
Author(s):  
Mitch Leslie
Keyword(s):  
Small Intestine ◽  
Tight Junction ◽  
Tight Junction Protein ◽  
Junction Protein

Researchers show how cells remove a tight junction protein to tweak small intestine permeability.

scholarly journals 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

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.

N ‐acetyl cysteine co‐treatment abates perfluorooctanoic acid‐induced reproductive toxicity in male rats

Andrologia ◽  
2021 ◽  
Author(s):  
Solomon E. Owumi ◽  
Ayomide P. Akomolafe ◽  
Innocent O. Imosemi ◽  
Oyeronke A. Odunola ◽  
Adegboyega K. Oyelere
Keyword(s):  
Reproductive Toxicity ◽  
Perfluorooctanoic Acid ◽  
Male Rats ◽  
Acetyl Cysteine

GENETIC SUSCEPTIBILITY TO IBD OPERATES VIA CONTROL OF APICAL JUNCTIONAL COMPLEXES

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S30-S30
Author(s):  
Isabelle Hébert-Milette ◽  
Chloé Lévesque ◽  
Guy Charron ◽  
John Rioux
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Intestinal Inflammation ◽  
Protein Localization ◽  
Junctional Complex ◽  
Epithelial Permeability ◽  
3D Cultures ◽  
Apical Junctional Complex ◽  
Junction Protein ◽  
The Impact

Abstract Introduction Intestinal permeability is increased in unaffected 1st degree relatives of patients with inflammatory bowel disease (IBD), and is considered a risk factor for the development of IBD, likely increasing the interactions between intestinal microorganisms and the immune system. We recently reported that C1orf106, a gene located within a genomic region associated with IBD, regulates epithelial permeability. We further demonstrated that a rare coding variant within C1orf106 (p.Y333F) decreases protein stability and that lower levels of C1orf106 protein leads altered stability of adherens junctions (AJ) and to an increase in epithelial permeability. Hypothesis In addition to altering AJ, we believe that C1orf106 is also involved in the regulation of tight junction (TJ) formation, which also impacts epithelial permeability. Objectives The objectives of the project are to (a) validate the impact of C1orf106 on tight junctions and (b) verify the impact of C1orf106 IBD-associated variants on intestinal barrier integrity. Results We observed that knocking down the expression of C1orf106 in Caco-2 cells leads to a number of phenotypes in human epithelial monolayer (2D) and spheroid (3D) cultures that are associated with alterations in TJs. Specifically, when studying the dynamic reformation of TJ in 2D cultures after transient withdrawal of calcium, which is required for TJ stability, we observed that lower levels of C1orf106 resulted in (1) decreased recovery of barrier function as measured by transepithelial electrical resistance (TEER); (2) an alteration of tight junction protein localization; and (3) thickening of the circumferential actin belt. Moreover, in 3D cultures, we observed an altered spheroid formation associated with impaired epithelial polarization. In addition, our preliminary studies of human induced pluripotent stem cell (hiPSC)-derived epithelial cultures support that Y333F heterozygotes also have altered structure and function of their tight junctions. Conclusion Our observations indicate an important role of C1orf106 in apical junctional complex (AJC) formation likely mediated by a regulation of the circumferential actin belt. This can affect other functions of AJC, like the establishment of cell polarity. AJC formation is important for epithelial repair after an injury and its dysregulation impairs the formation of an impermeable epithelial barrier, which likely facilitates the passage of microorganisms and the induction and maintenance of intestinal inflammation.

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