Vitamin A and Retinoic Acid Exhibit Protective Effects on Necrotizing Enterocolitis by Regulating Intestinal Flora and Enhancing the Intestinal Epithelial Barrier

Xiao, Sa; Li, Qiuping; Hu, Kun; He, Yu; Ai, Qing; Hu, Liuhong; Yu, Jialin

doi:10.1016/j.arcmed.2018.04.003

Cited by 57 publications

(46 citation statements)

References 32 publications

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“…The rat model of NEC is a well‐established experimental animal model. We and others have demonstrated that this experimental protocol induces in animals signs of illness and intestinal inflammation that resemble those of clinical NEC in neonates . In our previous study, we confirmed that lactadherin affects the secretion of mucin 2, the expression of claudin 1 in the intestine, and the permeability of the intestinal mucosa in an RV‐infected neonatal rat model .…”

Section: Discussionsupporting

confidence: 82%

Role of lactadherin in intestinal barrier integrity in experimental neonatal necrotizing enterocolitis

Shen

Lei

et al. 2019

J of Cellular Biochemistry

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Necrotizing enterocolitis (NEC) is one of the most widespread and devastating gastrointestinal diseases in neonates. Destruction of the intestinal barrier is the main underlying cause of NEC. The aim of this study was to determine the role of lactadherin in preventing NEC in a neonatal rat model and investigate the molecular mechanism of lactadherin-mediated protection of the intestinal barrier. Neonatal rats were divided into three groups: dam feeding (DF), NEC (NEC), and NEC supplemented with 10 μg/(g·day) recombinant human lactadherin (NEC+L). Intestinal permeability, tissue damage, and cell junction protein expression and localization were evaluated. We found that lactadherin reduced weight loss caused by NEC, reduced the incidence of NEC from 100% to 46.7%, and reduced the mean histological score for tissue damage to 1.40 compared with 2.53 in the NEC group. Intestinal permeability of lactadherintreated rats was significantly reduced when compared with that of the NEC group. In addition, the expression levels of JAM-A, claudin 3, and E-calcium in the ileum of NEC group animals increased compared with those in the ileum of DF group animals, and these levels decreased in the NEC+L group.Lactadherin changed the localization of claudin 3, occludin, and E-cadherin in epithelial cells. The mechanism underlying lactadherin-mediated protection of the intestinal barrier might be restoring the correct expression levels and localization of tight junction and adherent junction proteins. These findings suggest a new candidate agent for the prevention of NEC in newborns. K E Y W O R D Scell junctions, intestinal barrier, lactadherin, necrotizing enterocolitis, permeability SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.

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Section: Discussionsupporting

confidence: 82%

Role of lactadherin in intestinal barrier integrity in experimental neonatal necrotizing enterocolitis

Shen

Lei

et al. 2019

J of Cellular Biochemistry

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“…What's more, the levels of inflammatory factors were significantly reduced, while the expression levels of claudin-1, occludin, and ZO-1 were increased, leading to increase intestinal barrier function after the VA and RA treatments. Meanwhile, TEER was increased and lipopolysaccharide-induced damage was reduced in CaCO2 cell monolayers after RA treatment both in vivo and in vitro (27). In addition, our results further showed that ATRAinduced barrier function by inducing MUC2, not villin, expression.…”

Section: Discussionsupporting

confidence: 59%

All-Trans Retinoic Acid, A Derivative of Vitamin A, Improved Intestinal Epithelial Barrier Function Through PFKP

Xie¹,

Huang²,

Liu³

et al. 2020

Preprint

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Objective: Mucosal Healing, relied on the coordinated activity of IECs for improvement of intestinal barrier function, is the critical goal in treatment of IBD. All-trans retinoic acid (ATRA) is known to regulates cell proliferation and differentiation. The aims of the present study were to investigate the effects of ATRA on the intestinal differentiation. Methods: We collected the clinical sample from the patients to analyze the vitamin A, TEER, western blotting and real-time PCR were performed to detect the effect of vitamin A on PFKP expression and intestinal epithelial cell differentiation. Results: In this study, we showed that increased TEER and decrease paracellular permeability of IECs were induced by ATRA in dose-dependent manner, which is attributed to enhanced MUC2 expression, a marker of goblet cell by western blotting, real-time PCR and TEER assay, while no significant difference of villin was found to alter. The further results show that ATRA suppressed PFKP expression in IECs, while overexpression of PFKP could reverse the promotion of ATRA on MUC2 expression, implying ATRA-induced MUC2 expression in PFKP-dependent manner and in dose-dependent way. The clinical sample analysis suggested vitamin A is not significant associated with gender, and replenishment of vitamin A is critical for intestinal differentiation. Conclusion: ATRA improved intestinal epithelial differentiation via PFKP-mediated Muc2 expression. The findings suggest that ATRA could serve as a novel therapeutic agent to ameliorate development of inflammatory bowel disease. Keywords : All-trans Retinoic Acid; Muc2; Differentiation; PFKP; Intestinal Barrier Function

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“…Newborn C57BL/6J mice were purchased from the Animal Experiment Center of Chongqing Medical University (Chongqing, China). The NEC mouse model was previously described by Garg et al (2015), Li et al (2017), and Xiao et al (2018) and was adopted here with some modifications: 7-day-old C57BL/6 newborn mice were randomly separated into two groups. The control group was breast-fed with their mothers, and the experimental group was fed with formula milk (2 g of Similac Advance in 10 ml of 33% Esbilac puppy milk replacer) (Zeng et al, 2017) at 30 µl/1 g body weight every 4 h with a silicone tube (1.9 Fr) for 3 days.…”

Section: Neonatal Necrotizing Enterocolitis Mouse Modelmentioning

confidence: 99%

Autoinducer-2 May Be a New Biomarker for Monitoring Neonatal Necrotizing Enterocolitis

Yang

et al. 2020

Front. Cell. Infect. Microbiol.

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Autoinducer-2 (AI-2) has a widely accepted role in bacterial intra-and interspecies communication. Little is known about the relationships between AI-2 and NEC. This study found that AI-2 levels in patients and in a NEC mouse model were detected using the Vibrio harveyi BB170 assay system. Bacterial communities of the newborns' stool microbiota (NEC acute group, NEC recovery group, control group, and antibiotics-free group) and of the NEC mouse model (NEC group and control group) were detected by high-throughput sequencing. Intestinal histopathological changes were observed after HE staining. The AI-2 level in the NEC acute group (44.75 [40.17∼65.52]) was significantly lower than that in the control group, NEC recovery group and antibiotics-free group. The overall microbiota compositions of each group at the phylum level were not significantly different. The proportions of Enterococcus, Clostridium_sensu_stricto_1, Peptoclostridium, and Veillonella had significant differences among the 4 groups at the genus level. In animal experiments, the AI-2 level in feces of NEC mice (56.89 ± 11.87) was significantly lower than that in the feces of control group mice (102.70 ± 22.97). The microbiota compositions of NEC and control group mice at the phylum level were not significantly different. At the genus level, Klebsiella, Clostridium_sensu_stricto_1, and Peptoclostridium abundances in the NEC group increased significantly compared with those in the control group (P < 0.05). In addition, Lactobacillus, Pasteurella, and Parabacteroides abundances in the NEC group decreased significantly compared with those in the normal control group (P < 0.05), while Lactobacillus, Pasteurella, and Parabacteroides abundances had the opposite trend. The AI-2 concentration decreased significantly in the acute phase of NEC and increased gradually in the convalescent phase. We conclude that the concentration of AI-2 was correlated with intestinal flora disorder and different stages of disease. AI-2 may be a new biomarker for the diagnosis and monitoring of NEC.

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Vitamin A and Retinoic Acid Exhibit Protective Effects on Necrotizing Enterocolitis by Regulating Intestinal Flora and Enhancing the Intestinal Epithelial Barrier

Cited by 57 publications

References 32 publications

Role of lactadherin in intestinal barrier integrity in experimental neonatal necrotizing enterocolitis

Role of lactadherin in intestinal barrier integrity in experimental neonatal necrotizing enterocolitis

All-Trans Retinoic Acid, A Derivative of Vitamin A, Improved Intestinal Epithelial Barrier Function Through PFKP

Autoinducer-2 May Be a New Biomarker for Monitoring Neonatal Necrotizing Enterocolitis

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