Naringenin enhances intestinal barrier function through the expression and cytoskeletal association of tight junction proteins in Caco-2 cells

Noda, Sakino; Tanabe, Soichi; Suzuki, Takuya

doi:10.1002/mnfr.201300045

Cited by 69 publications

(59 citation statements)

References 42 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Depletion of polyamines disrupts TJs permeability via JunD dependent negative regulation of ZO-1 gene (Chen et al, 2008). Sodium butyrate and Naringenin enhances barrier functions through increased expression of Cldn-1 and Cldn-4, respectively, via transcription factor SP-1 (Wang et al, 2012; Noda et al, 2013). Loss of Hnf4A affects colonic ions transport via down regulation of Cldn-15 and causes IBD type chronic inflammation in mice (Darsigny et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2 Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients

et al. 2017

View full text Add to dashboard Cite

Mycophenolic acid (MPA) is prescribed to prevent allograft rejection in organ transplanted patients. However, its use is sporadically linked to leak flux diarrhea and other gastrointestinal (GI) disturbances in around 75% of patients through yet unknown mechanisms. Recently, we identified Midkine as a modulator of tight junctions (TJs) permeability in MPA treated Caco-2 monolayer. In the present study, we investigated the possible involvement of Midkine dependent PI3K pathway in alteration of TJs under MPA treatment. Caco-2 cells were grown as monolayer to develop TJs and were treated for 72 h with DMSO (control) or MPA in presence and absence of Midkine inhibitor (iMDK) or PI3K inhibitors (LY/AMG). Caco-2 monolayer integrity was assessed by transepithelial electrical resistance (TEER) and FITC-dextran assays. Our functional assays showed that PI3K inhibitors (LY/AMG) can significantly inhibit the compromised TJs integrity of MPA-treated Caco-2 cells monolayer. Chromatin immunoprecipitation analyses showed a significant epigenetic activation of Midkine, PI3K, Cdx-2, and Cldn-2 genes and epigenetic repression of Cldn-1 gene after MPA treatment. The MPA-induced epigenetic alterations were further confirmed by mRNA and protein expression analysis. Collectively, our data shows that PI3K pathway as the downstream target of Midkine which in turn modulates p38MAPK and pAKT signaling to alter TJs permeability in Caco-2 cell monolayers treated with MPA. These results highlight the possible use of either Midkine or PI3K inhibitors as therapeutic agents to prevent MPA induced GI disturbances.

show abstract

Section: Discussionmentioning

confidence: 99%

MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2 Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Whole cell and detergent-insoluble fractions were prepared as described previously [11]. Briefly, whole cell protein lysates and detergent-insoluble fractions were prepared in a modified RIPA buffer containing proteinase inhibitors and phosphatase inhibitors as described elsewhere [12].…”

Section: Methodsmentioning

confidence: 99%

Fermented barley and soybean (BS) mixture enhances intestinal barrier function in dextran sulfate sodium (DSS)-induced colitis mouse model

Woo

Choi

Kang

et al. 2016

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundInflammatory bowel disease (IBD) is characterized by chronic or relapsing immune system activation and inflammation within the gastrointestinal tract. The lack of safety and efficacy of standard therapies, the use of food supplements for managing IBD is increasing, and many studies have reported that various food supplements provide many beneficial effects for the IBD.MethodsThis study aimed to evaluate the anti-colitis effects of dietary supplementation with a fermented barley and soybean mixture (BS) on intestinal inflammation using a murine model of IBD. Female C57BL/6 mice were administered with either BS (100 and 200 mg/kg/day) or vehicle (PBS) control through oral gavages for 3 days and received 5% dextran sulfate sodium (DSS) drinking water to induce colitis. Mice body weight was measured every two days and disease activity index (DAI) score was determined on Day 15; mice were sacrificed and colons were analyzed by H & E staining and RT-PCR. We also measured intestinal barrier function in vitro using DSS-treated Caco-2 cells by assessing ZO-1 immunofluorescence staining and Western blotting and in vivo by measuring serum level of FITC-Dextran and by performing bacteria culture from mesenteric lymph nodes (MLN) extract. The gut microbiota was examined by real time PCR using fecal DNA.ResultsWe found that BS alleviated the severity of colitis in a DSS-induced colitis mouse model, and suppressed levels of pro-inflammatory cytokines in colonic tissue. Moreover, BS prevented epithelial barrier dysfunction, inducing an increase of tight junction protein levels in colonic tissues, BS also inhibited FITC-dextran permeability, and suppressed bacterial translocation to MLNs. In addition, BS increased the levels of Lactobacilli and Bacteroides, which have anti-inflammatory properties.ConclusionOur study suggests that BS has protective roles against inflammatory bowel disease through changes in inflammatory activity, tight junction protein expression, and gut microbiota composition in DSS-induced colitis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1479-0) contains supplementary material, which is available to authorized users.

show abstract

“…162 This was also observed with the flavonone naringenin (10-100 mM). 163 By contrast, studies in vitro have shown that the polyphenol flavonoid quercetin (30-100 mM), as well as other flavonoids like flavone (150 mM), kaempferol (100 mM), and genistein (100 mM), are potent inhibitors of iHSPs (especially iHSP70). [164][165][166] Luteolin (25 mM) was a weak inhibitor of iHSP70, and rutin had no effect.…”

Section: Flavonoidsmentioning

confidence: 99%

Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota

Arnal

Lallès

2016

Nutr Rev

View full text Add to dashboard Cite

Naringenin enhances intestinal barrier function through the expression and cytoskeletal association of tight junction proteins in Caco-2 cells

Cited by 69 publications

References 42 publications

MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2 Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients

MPA Modulates Tight Junctions' Permeability via Midkine/PI3K Pathway in Caco-2 Cells: A Possible Mechanism of Leak-Flux Diarrhea in Organ Transplanted Patients

Fermented barley and soybean (BS) mixture enhances intestinal barrier function in dextran sulfate sodium (DSS)-induced colitis mouse model

Gut epithelial inducible heat-shock proteins and their modulation by diet and the microbiota

Contact Info

Product

Resources

About