scholarly journals MiR-126 impairs the intestinal barrier function via inhibiting S1PR2 mediated activation of PI3K/AKT signaling pathway

2017 ◽  
Author(s):  
Tanzhou Chen ◽  
Haibo Xue ◽  
Ruoyang Lin ◽  
Zhiming Huang
Keyword(s):  
Signaling Pathway ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Akt Signaling ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Intestinal Mucosal Barrier ◽  
Pathological Tissues

AbstractBackgroundAberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD.MethodsIn this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2. The transendothelial electrical resistance assay was used to measured the value of TEER.ResultsThe expressions of miR-126, S1PR2 and S1P in the pathological tissues of IBD patients were significantly higher than that of the control group. Moreover, miR-126 overexpression contributed to intestinal mucosal barrier dysfunction in vitro. S1PR2 was a direct target of miR-126, and S1PR2 expression was negatively regulated by miR-126 in Caco-2 cells. However, S1PR2 activated by S1P had the protection effect for the integrity and permeability of intestinal mucosal barrier via a PI3K/Akt dependent mechanism. MiR-126 silencing possessed obvious protective effects on the intestinal barrier function, but these effects could be reversed by JTE-013 or LY294002.ConclusionMiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.

scholarly journals Chitosan Ameliorates DSS-Induced Ulcerative Colitis Mice by Enhancing Intestinal Barrier Function and Improving Microflora

2019 ◽  
Vol 20 (22) ◽  
pp. 5751 ◽  
Author(s):  
Jia Wang ◽  
Cuili Zhang ◽  
Chunmei Guo ◽  
Xinli Li
Keyword(s):  
Barrier Function ◽  
Intestinal Microflora ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Tight Junction Proteins ◽  
Intestinal Mucosal Barrier ◽  
Tnf Α ◽  
Mucosal Barrier Function ◽  
Junction Proteins

Ulcerative colitis (UC) has been identified as one of the inflammatory diseases. Intestinal mucosal barrier function and microflora play major roles in UC. Modified-chitosan products have been consumed as effective and safe drugs to treat UC. The present work aimed to investigate the effect of chitosan (CS) on intestinal microflora and intestinal barrier function in dextran sulfate sodium (DSS)-induced UC mice and to explore the underlying mechanisms. KM (Kunming) mice received water/CS (250, 150 mg/kg) for 5 days, and then received 3% DSS for 5 days to induce UC. Subsequently, CS (250, 150 mg/kg) was administered daily for 5 days. Clinical signs, body weight, colon length, and histological changes were recorded. Alterations of intestinal microflora were analyzed by PCR-DGGE, expressions of TNF-α and tight junction proteins were detected by Western blotting. CS showed a significant effect against UC by the increased body weight and colon length, decreased DAI (disease activity index) and histological injury scores, and alleviated histopathological changes. CS reduced the expression of TNF-α, promoted the expressions of tight junction proteins such as claudin-1, occludin, and ZO-1 to maintain the intestinal mucosal barrier function for attenuating UC in mice. Furthermore, Parabacteroides, Blautia, Lactobacillus, and Prevotella were dominant organisms in the intestinal tract. Blautia and Lactobacillus decreased with DSS treatment, but increased obviously with CS treatment. This is the first time that the effect of original CS against UC in mice has been reported and it is through promoting dominant intestinal microflora such as Blautia, mitigating intestinal microflora dysbiosis, and regulating the expressions of TNF-α, claudin-1, occludin, and ZO-1. CS can be developed as an effective food and health care product for the prevention and treatment of UC.

scholarly journals Intestinal Mucosal Barrier Function Restoration in Mice by Maize Diet Containing Enriched Flavan-4-Ols

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 896 ◽  
Author(s):  
Binning Wu ◽  
Rohil Bhatnagar ◽  
Vijaya V. Indukuri ◽  
Shara Chopra ◽  
Kylie March ◽  
...  
Keyword(s):  
Barrier Function ◽  
Control Diet ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Low Grade ◽  
Colonic Inflammation ◽  
Mucosal Barrier Function ◽  
Inflammatory Bowel ◽  
Histology Score

Inflammatory bowel disease (IBD), a chronic intestinal inflammatory condition, awaits safe and effective preventive strategies. Naturally occurring flavonoid compounds are promising therapeutic candidates against IBD due to their great antioxidant potential and ability to reduce inflammation and improve immune signaling mediators in the gut. In this study, we utilized two maize near-isogenic lines flavan-4-ols-containing P1-rr (F+) and flavan-4-ols-lacking p1-ww (F−) to investigate the anti-inflammatory property of flavan-4-ols against carboxymethylcellulose (CMC)-induced low-grade colonic inflammation. C57BL/6 mice were exposed to either 1% CMC (w/v) or water for a total of 15 weeks. After week six, mice on CMC treatment were divided into four groups. One group continued on the control diet. The second and third groups were supplemented with F+ at 15% or 25% (w/w). The fourth group received diet supplemented with F− at 15%. Here we report that mice consuming F+(15) and F+(25) alleviated CMC-induced increase in epididymal fat-pad, colon histology score, pro-inflammatory cytokine interleukin 6 expression and intestinal permeability compared to mice fed with control diet and F−(15). F+(15) and F+(25) significantly enhanced mucus thickness in CMC exposed mice (p < 0.05). These data collectively demonstrated the protective effect of flavan-4-ol against colonic inflammation by restoring intestinal barrier function and provide a rationale to breed for flavan-4-ols enriched cultivars for better dietary benefits.

scholarly journals MicroRNA-561 Affects Proliferation and Cell Cycle Transition Through PTEN/AKT Signaling Pathway by Targeting P-REX2a in NSCLC

2020 ◽  
Vol 28 (2) ◽  
pp. 147-159 ◽  
Author(s):  
ZiJun Liao ◽  
Qi Zheng ◽  
Ting Wei ◽  
YanBing Zhang ◽  
JieQun Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Nsclc Cell ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Proliferation And Metastasis ◽  
Exogenous Expression ◽  
Induced Apoptosis

MicroRNAs (miRNAs) play crucial roles in tumorigenesis and tumor progression. miR-561 has been reported to be downregulated in gastric cancer and affects cancer cell proliferation and metastasis. However, the role and underlying molecular mechanism of miR-561 in human non-small cell lung cancer (NSCLC) remain unknown and need to be further elucidated. In this study, we discovered that miR-561 expression was downregulated in human NSCLC tissues and cell lines. The overexpression of miR-561 inhibited NSCLC cell proliferation and cell cycle G1/S transition and induced apoptosis. The inhibition of miR-561 facilitated cell proliferation and G1/S transition and suppressed apoptosis. miR-561 expression was inversely correlated with P-REX2a expression in NSCLC tissues. P-REX2a was confirmed to be a direct target of miR-561 using a luciferase reporter assay. The overexpression of miR-561 decreased P-REX2a expression, and the suppression of miR-561 increased P-REX2a expression. Particularly, P-REX2a silencing recapitulated the cellular and molecular effects observed upon miR-561 overexpression, and P-REX2a overexpression counteracted the effects of miR-561 overexpression on NSCLC cells. Moreover, both exogenous expression of miR-561 and silencing of P-REX2a resulted in suppression of the PTEN/AKT signaling pathway. Our study demonstrates that miR-561 inhibits NSCLC cell proliferation and G1/S transition and induces apoptosis through suppression of the PTEN/AKT signaling pathway by targeting P-REX2a. These findings indicate that miR-561 plays a significant role in NSCLC progression and serves as a potential therapeutic target for NSCLC.

scholarly journals Downregulation of microRNA-149 in retinal ganglion cells suppresses apoptosis through activation of the PI3K/Akt signaling pathway in mice with glaucoma

2018 ◽  
Vol 315 (6) ◽  
pp. C839-C849 ◽  
Author(s):  
Xin-Gang Nie ◽  
Dong-Sheng Fan ◽  
Yan-Xia Huang ◽  
Ying-Ying He ◽  
Bo-Li Dong ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Ultrastructural Changes ◽  
Retinal Ganglion ◽  
Akt Signaling Pathway ◽  
Luciferase Reporter Gene ◽  
Gene Assay

Glaucoma represents a major cause of blindness, generally associated with elevated intraocular pressure (EIOP). The aim of the present study was to investigate whether microRNA-149 (miR-149) affects retinal ganglion cells (RGCs) and the underlying mechanism based on a mouse model of chronic glaucoma with EIOP. The successfully modeled mice were administered with mimics or inhibitors of miR-149. Next, the number of RGCs, ultrastructural changes of RGCs, and purity of RGCs in the retinal tissues were detected. Moreover, the RGCs were collected and subsequently treated with 60 mmHg pressure and transfected with a series of plasmids aiding in the regulation of the expression of miR-149 and betacellulin (BTC). The levels of miR-149, BTC, phosphatidylinositol 3-kinase (PI3K), and Akt were subsequently determined. Finally, RGC viability and apoptosis were detected accordingly. Dual luciferase reporter gene assay provided validation, highlighting BTC was indeed a target gene of miR-149. The downregulation of miR-149 is accompanied by an increased number of RGCs and decreased ultrastructural RGC alterations. Additionally, downregulated miR-149 was noted to increase the levels of BTC, PI3K, and Akt in both the retinal tissues and RGCs, whereas the silencing of miR-149 was observed to promote the viability of RGC and inhibit RGC apoptosis. Taken together, the results of the current study provided validation suggesting that the downregulation of miR-149 confers protection to RGCs by means of activating the PI3K/Akt signaling pathway via upregulation of BTC in mice with glaucoma. Evidence presented indicated the promise of miR-149 inhibition as a potential therapeutic strategy for glaucoma treatment.

scholarly journals Macrophage Deficiency Makes Intestinal Epithelial Cells Susceptible to NSAID-Induced Damage

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xinxin Wang ◽  
Jiayang Wang ◽  
Tianyu Xie ◽  
Shuo Li ◽  
Di Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Epithelial Proliferation ◽  
Gm Csf ◽  
Mucosal Barrier Function

Objectives. In Crohn’s disease (CD), the mechanisms underlying the regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of mucosal barrier function in the ileum are unclear. We analyzed the molecular mechanisms underlying the regulation by GM-CSF of the mucosal barrier function. Methods. We examined the role of GM-CSF in the intestinal barrier function in CD at the molecular-, cellular-, and animal-model levels. Results. Macrophages directly secreted GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis, which maintained intestinal barrier function. Macrophages were absent in NSAID-induced ileitis, causing GM-CSF deficiency, increasing the apoptosis rate, decreasing the proliferation rate, increasing inter- and paracellular permeabilities, decreasing the TJP levels, and reducing the numbers of mesenteric lymph nodes, memory T cells, and regulatory T cells in Csf1op/op transgenic mice. Conclusions. GM-CSF is required for the maintenance of intestinal barrier function. Macrophages directly secrete GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis.

Bioactive factors secreted by Bifidobacterium breve B-3 enhance barrier function in human intestinal Caco-2 cells

2019 ◽  
Vol 10 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Y. Kurose ◽  
J. Minami ◽  
A. Sen ◽  
N. Iwabuchi ◽  
F. Abe ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Barrier Function ◽  
Promoter Activity ◽  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Luciferase Reporter ◽  
Barrier Integrity ◽  
Bifidobacterium Breve ◽  
Enhancing Effect

Intestinal barrier function is closely related to intestinal health and diseases. Recent studies demonstrate that some probiotic and commensal bacteria secrete metabolites that are capable of affecting the intestinal functions. The present study examined an enhancing effect of bioactive factors secreted by Bifidobacterium breve strain B-3 on the intestinal tight junction (TJ) barrier integrity in human intestinal Caco-2 cells. Administration of conditioned medium obtained from B. breve strain B-3 (B3CM) to Caco-2 cells for 24 h increased trans-epithelial electrical resistance (TER), a TJ barrier indicator, across their monolayers. Immunoblot, immunofluorescence, and qPCR analyses demonstrated that B3CM increased an integral TJ protein, claudin-4 expression. In luciferase reporter assay, the administration of B3CM enhanced the claudin-4 promoter activity, indicating the transcriptional upregulation of claudin-4. Site-directed mutation of specificity protein 1 (Sp1) binding sites in the claudin-4 promoter sequence and suppression of Sp1 expression by siRNA technology clearly reduced the enhancing effect of B3CM on claudin-4 promoter activity. Liquid chromatography/mass spectrometry detected a significant amount of acetic acid in B3CM (28.3 mM). The administration of acetic acid to Caco-2 cells partially mimicked a B3CM-mediated increase in TER, but failed to increase claudin-4 expression. Taken together, bioactive factors secreted by B. breve B-3 enhanced the TJ barrier integrity in intestinal Caco-2 cells. Transcriptional regulation of claudin-4 through Sp1 is at least in part one of the underlying molecular mechanisms. In addition, acetic acid contributes to the B3CM-mediated barrier effect independently of claudin-4 expression.

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