scholarly journals TNF-α–Induced miR-21-3p Promotes Intestinal Barrier Dysfunction by Inhibiting MTDH Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhifeng Jiang ◽  
Feiyu Yang ◽  
Jingbo Qie ◽  
Chaoyuan Jin ◽  
Feng Zhang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Wnt Signaling Pathway ◽  
Intestinal Barrier ◽  
Pathological Process ◽  
Dependent Manner ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Potential Biomarker ◽  
Tnf Α ◽  
Cancer Tumor

Intestinal barrier dysfunction is characterized by increased intestinal permeability to lumen endotoxin, showing remarkable predisposition to immune enteropathy, and colorectal cancer tumor necrosis factor (TNF)-α is associated with this pathological process, while the mechanism remains unknown. In this study, different doses of TNF-α were used for Caco-2 cell treatment. We discovered that miR-21-3p expression was obviously increased by TNF-α in a dose-dependent manner. Further study demonstrated that TNF-α could upregulate miR-21-3p expression through the NF-κB signaling pathway. Then, TargetScan and miRWalk miRNA–mRNA interaction prediction online tools were introduced, and metadherin (MTDH) was screened out as a potential target of miR-21-3p. We subsequently found that miR-21-3p could directly target the 3′-untranslated region (UTR) of MTDH mRNA and inhibit its expression. Furthermore, it was demonstrated that miR-21-3p could regulate the Wnt signaling pathway by targeting MTDH mRNA, suggesting the effect of miR-21-3p/MTDH/Wnt axis on intestinal barrier dysfunction. Our findings provide a novel potential biomarker and therapeutic target for intestinal barrier dysfunction and related diseases.

scholarly journals Association of Hyperuricemia With Immune Disorders and Intestinal Barrier Dysfunction

2020 ◽  
Vol 11 ◽  
Author(s):  
Qiulan Lv ◽  
Daxing Xu ◽  
Xuezhi Zhang ◽  
Xiaomin Yang ◽  
Peng Zhao ◽  
...  
Keyword(s):  
Uric Acid ◽  
Gut Microbiota ◽  
Intestinal Barrier ◽  
Urate Oxidase ◽  
Intestinal Immunity ◽  
Immune Disorders ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Gut Barrier Function ◽  
Tnf Α

BackgroundMore than 30–40% of uric acid is excreted via the intestine, and the dysfunction of intestinal epithelium disrupts uric acid excretion. The involvement of gut microbiota in hyperuricemia has been reported in previous studies, but the changes and mechanisms of intestinal immunity in hyperuricemia are still unknown.MethodsThis study developed a urate oxidase (Uox)-knockout (Uox–/–) mouse model for hyperuricemia using CRISPR/Cas9 technology. The lipometabolism was assessed by measuring changes in biochemical indicators. Furthermore, 4-kDa fluorescein isothiocyanate–labeled dextran was used to assess gut barrier function. Also, 16S rRNA sequencing was performed to examine the changes in gut microbiota in mouse feces. RNA sequencing, Western blot, Q-PCR, ELISA, and immunohistochemical analysis were used for measuring gene transcription, the number of immune cells, and the levels of cytokines in intestinal tissues, serum, kidney, liver, pancreas, and vascellum.ResultsThis study showed that the abundance of inflammation-related microbiota increased in hyperuricemic mice. The microbial pattern recognition–associated Toll-like receptor pathway and inflammation-associated TNF and NF-kappa B signaling pathways were significantly enriched. The increased abundance of inflammation-related microbiota resulted in immune disorders and intestinal barrier dysfunction by upregulating TLR2/4/5 and promoting the release of IL-1β and TNF-α. The levels of epithelial tight junction proteins occludin and claudin-1 decreased. The expression of the pro-apoptotic gene Bax increased. The levels of LPS and TNF-α in systemic circulation increased in hyperuricemic mice. A positive correlation was observed between the increase in intestinal permeability and serum levels of uric acid.ConclusionHyperuricemia was characterized by dysregulated intestinal immunity, compromised intestinal barrier, and systemic inflammation. These findings might serve as a basis for future novel therapeutic interventions for hyperuricemia.

Biogenic selenium nanoparticles synthesized by Lactobacillus casei ATCC 393 alleviate diquat-induced intestinal barrier dysfunction in C57BL/6 mice through their antioxidant activity

2020 ◽  
Vol 11 (4) ◽  
pp. 3020-3031 ◽  
Author(s):  
Lei Qiao ◽  
Xina Dou ◽  
Shuqi Yan ◽  
Baohua Zhang ◽  
Chunlan Xu
Keyword(s):  
Antioxidant Activity ◽  
Oxidative Damage ◽  
Signaling Pathway ◽  
Lactobacillus Casei ◽  
Intestinal Barrier ◽  
Selenium Nanoparticles ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Nrf2 Signaling Pathway ◽  
Biogenic Selenium Nanoparticles

Biogenic SeNPs synthesized by Lactobacillus casei ATCC 393 reversed diquat-induced oxidative damage to the epithelium by activating the Nrf2 signaling pathway.

scholarly journals Protective Role of Somatostatin in Sepsis-Induced Intestinal Barrier Dysfunction through Inhibiting the Activation of NF-κB Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Xin Xu ◽  
Quanli Zhu ◽  
Guoliang Li ◽  
Junjian Ma ◽  
Zhijian Pan ◽  
...  
Keyword(s):  
Protective Effect ◽  
Somatostatin Receptor ◽  
Intestinal Barrier ◽  
Protective Role ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Drug ◽  
Receptor Subtype ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Tnf Α

Somatostatin (SST) has a protective role in intestinal injury, inflammatory response, and intestinal mucosal barrier in rats with acute pancreatitis. However, its function in sepsis-induced intestinal barrier dysfunction remains largely unknown. A mouse sepsis model was constructed, and SST was injected into the tail vein. Then, hematoxylin and eosin staining (HE) was used to detect the intestinal barrier dysfunction. Enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor α- (TNF-) α, interleukin- (IL-) 6, and interleukin- (IL-) 10 in the ileum. Expressions of tight junction proteins, zonula occludens- (ZO-) 1 and Claudin-1, and NF-κB p65 in the ileum were detected using western blot and immunohistochemistry as needed. Furthermore, JSH-23 as an inhibitor of the NF-κB pathway was injected into sepsis mice with SST or not. Mice with sepsis showed an obvious intestinal barrier dysfunction with decreasing specific somatostatin receptor subtype (SSTRs), and increasing TNF-α, IL-6, and IL-10 in the ileum. SST could relieve the injury, the decrease of SSTRs, and the increase of TNF-α and IL-6 induced by sepsis and also further enhanced the expression of IL-10. Further analysis showed that ZO-1 and Claudin-1 were reduced in the ileum by sepsis but enhanced by SST. NF-κB p65 was promoted in the ileum by sepsis but inhibited by SST. Further experiments confirmed that NF-κB inhibitor JSH-23 could repair the intestinal barrier dysfunction and enhance the protective effect of SST on the intestinal barrier. SST, with a protective effect on intestinal barrier dysfunction through suppression of NF-κB, could be a potential therapeutic drug for sepsis-induced intestinal barrier dysfunction.

In-Depth Study of Transmembrane Mucins in Association with Intestinal Barrier Dysfunction During the Course of T Cell Transfer and DSS-Induced Colitis

2020 ◽  
Vol 14 (7) ◽  
pp. 974-994 ◽  
Author(s):  
Tom Breugelmans ◽  
Hanne Van Spaendonk ◽  
Joris G De Man ◽  
Heiko U De Schepper ◽  
Aranzazu Jauregui-Amezaga ◽  
...  
Keyword(s):  
T Cell ◽  
Intestinal Permeability ◽  
Intestinal Barrier ◽  
Transfer Model ◽  
Cell Transfer ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Tnf Α ◽  
Mucin Expression ◽  
T Cell Transfer

Abstract Background and Aims There is evidence for a disturbed intestinal barrier function in inflammatory bowel diseases [IBD] but the underlying mechanisms are unclear. Because mucins represent the major components of the mucus barrier and disturbed mucin expression is reported in the colon of IBD patients, we studied the association between mucin expression, inflammation and intestinal permeability in experimental colitis. Methods We quantified 4-kDa FITC-dextran intestinal permeability and the expression of cytokines, mucins, junctional and polarity proteins at dedicated time points in the adoptive T cell transfer and dextran sodium sulfate [DSS]-induced colitis models. Mucin expression was also validated in biopsies from IBD patients. Results In both animal models, the course of colitis was associated with increased interleukin-1β [IL-1β] and tumour necrosis factor-α [TNF-α] expression and increased Muc1 and Muc13 expression. In the T cell transfer model, a gradually increasing Muc1 expression coincided with gradually increasing 4-kDa FITC-dextran intestinal permeability and correlated with enhanced IL-1β expression. In the DSS model, Muc13 expression coincided with rapidly increased 4-kDa FITC-dextran intestinal permeability and correlated with TNF-α and Muc1 overexpression. Moreover, a significant association was observed between Muc1, Cldn1, Ocln, Par3 and aPKCζ expression in the T cell transfer model and between Muc13, Cldn1, Jam2, Tjp2, aPkcζ, Crb3 and Scrib expression in the DSS model. Additionally, MUC1 and MUC13 expression was upregulated in inflamed mucosa of IBD patients. Conclusions Aberrantly expressed MUC1 and MUC13 might be involved in intestinal barrier dysfunction upon inflammation by affecting junctional and cell polarity proteins, indicating their potential as therapeutic targets in IBD.

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