• Title/Summary/Keyword: Claudin-3

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Inhibition of Cell Invasion by Ethyl Alcohol Extracts of Hizikia fusiforme in AGS Human Gastric Adenocarcinoma Cells (AGS 인체 위암세포에서 톳 에탄올 추출물에 의한 침윤성 저해)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.20 no.12
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    • pp.1784-1791
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    • 2010
  • In this study, we investigated the effects of ethyl alcohol extracts of Hizikia fusiforme (EHF) on the correlation between tightening of tight junctions (TJs) and anti-invasive activity in human gastric adenocarcinoma AGS cells. Inhibitory effects of EHF on cell proliferation, motility, and invasiveness were found to be associated with increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance. Activities of matrix metalloprotease (MMP)-2 and -9 in AGS cells were dose-dependently inhibited by treatment with EHF, and this was also correlated with a decrease in expression of their mRNA and proteins; however, tissue inhibitor of metalloproteinase (TIMP)-1 and -2 mRNA levels were increased. Additionally, immunoblotting results indicated that EHF repressed the levels of claudin proteins (claudin-1, -3, and -4), major components of TJs that play key roles in control and selectivity of paracellular transport. Furthermore, EHF decreased expression of insulin such as growth factor-1 receptor proteins, while concurrently increasing that of thrombospondin-1 and E-cadherin. In conclusion, these results suggest that EHF treatment may inhibit tumor cell motility and invasion, and therefore act as a dietary source to decrease the risk of cancer metastasis.

Investigation of the effect of Hibiscus sabdariffa L. extracts on tight-junction related genes in human keratinocyte HaCaT cells (히비스커스 추출물이 인간 각질 형성 세포의 밀착 연접 관련 유전자 발현에 미치는 영향 연구)

  • Jung, Haesoo;Kim, Eunmi;Han, Hyosang;Kim, Keekwang
    • The Korea Journal of Herbology
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    • v.36 no.5
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    • pp.59-67
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    • 2021
  • Objectives : Hibiscus (Hibiscus sabdariffa L.) is rich in antioxidants such as flavonoids and anthocyanins and is known to have anti-inflammatory activity and anti-aging function of the skin, but there is no study on its effect on the skin barrier. This study aim to investigate the positive effect on the skin barrier by confirming the effect of water extracts of Hibiscus sabdariffa L. (WEHS) on the tight junction-related gene expression. Methods : The antioxidant efficacy of WEHS was investigated through ABTS and DPPH assays, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium was performed to examine the effect on cell viability. quantitative Reverse transcription polymerase chain reaction and immunoblot analysis were performed to confirm the effect of WEHS on the expression of tight junction-related genes, and immunofluorescence microscopy was used to confirm the movement of Claudin 1 protein into tight junctions. Results : WEHS showed strong antioxidant activity and induced an increase in both mRNA and protein expression levels of Claudin 1 among tight junction-related genes. The strong localization of Claudine 1 protein increased by WEHS to the tight junction was confirmed by immunofluorescence microscopy. Conclusions : Hibiscus was confirmed through this study to show antioxidant activity and the function of promoting the expression of the tight junction Claudin 1 gene, suggesting that Hibiscus can be used as a material for the prevention and treatment of skin moisturizing and atopy, which have an important influence on tight junction.

Immunofluorescence Microscopic Evaluation of Tight Junctional Proteins during Enterotoxigenic Bacteroides fragilis (ETBF) Infection in Mice

  • Hwang, Soonjae;Kang, Yeowool;Jo, Minjeong;Kim, Sung Hoon;Cho, Won Gil;Rhee, Ki-Jong
    • Biomedical Science Letters
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    • v.24 no.3
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    • pp.275-279
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    • 2018
  • Inflammatory bowel disease (IBD) is increasing in prevalence in developed countries but the cause of this increase is unclear. In animal models of IBD and in human IBD patients, alterations in the tight junctional proteins have been observed, suggesting that the intestinal microflora may penetrate the underlying colonic tissue and promote inflammation. Enterotoxigenic Bacteroides fragilis (ETBF) causes inflammatory diarrhea in human and is implicated in inflammatory bowel diseases. However, it is unclear whether alterations in tight junctional proteins occur during ETBF infection in mice. In this brief communication, we report that ETBF infection induces up-regulation of claudin-2 and down-regulation of claudin-5 through B. fragilis toxin (BFT) activity in the large intestine of C57BL/6 mice. In contrast, BFT did not induce changes in tight junctional proteins in the HT29/C1 cell line, suggesting that analysis of biological activity of BFT in vivo is important for evaluating ETBF effects.

Effect of a Hot Water Extract of Sparasis Crispa on the Expression of Tight Junction-Associated Genes in HaCaT Cells (꽃송이버섯 열수추출물이 HaCaT의 세포 연접 관련 유전자의 발현에 대한 영향)

  • Han, Hyo-Sang
    • Journal of The Korean Society of Integrative Medicine
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    • v.9 no.2
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    • pp.83-92
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    • 2021
  • Purpose : Keratinocytes are the main cellular components involved in wound healing during re-epithelization and inflammation. Dysfunction of tight junction (TJ) adhesions is a major feature in the pathogenesis of various diseases. The purpose of this study was to identify the various effects of a Sparassis crispa water extract (SC) on HaCaT cells and to investigate whether these effects might be applicable to human skin. Methods : We investigated the effectiveness of SC on cell HaCaT viability using MTS. The antioxidant effect of SC was analyzed by comparing the effectiveness of ABTS to that of the well-known antioxidant resveratrol. Reverse-transcription quantitative polymerase chain reaction (qRT-PCR) is the most widely applied method Quantitative RT-PCR analysis has shown that SC in HaCaT cells affects mRNA expression of tight-junction genes associated with skin moisturization. In addition, Wound healing is one of the most complex processes in the human body. It involves the spatial and temporal synchronization of a variety of cell types with distinct roles in the phases of hemostasis, inflammation, growth, re-epithelialization, and remodeling. wound healing analysis demonstrated altered cell migration in SC-treated HaCaT cells. Results : MTS analysis in HaCaT cells was found to be more cytotoxic in SC at a concentration of 0.5 mg/㎖. Compared to 100 µM resveratrol, 4 mg/㎖ SC exhibited similar or superior antioxidant effects. SC treatment in HaCaT cells reduced levels of claudin 1, claudin 3, claudin 4, claudin 6, claudin 7, claudin 8, ZO-1, ZO-2, JAM-A, occludin, and Tricellulin mRNA expression by about 1.13 times. Wound healing analysis demonstrated altered cell migration in SC-treated HaCaT cells and HaCaT cell migration was also reduced to 73.2 % by SC treatment. Conclusion : SC, which acts as an antioxidant, reduces oxidative stress and prevents aging of the skin. Further research is needed to address the effects of SC on human skin given the observed alteration of mRNA expression of tight-junction genes and the decreased the cell migration of HaCaT cells.

Inhibition of Cell Invasion by Indole-3-Carbinol in OVCAR-3 Human Ovarian Cancer Cells (Indole-3-carbinol에 의한 OVCAR-3 인체 난소암세포의 침윤 억제)

  • Choi, Yung-Hyun;Kim, Sung-Ok
    • Journal of Life Science
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    • v.21 no.7
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    • pp.923-931
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    • 2011
  • In the present study, we investigated the effect of indole-3-carbinol (I3C), a natural compound present in vegetables, on the cell migration and invasion of OVCAR-3 ovarian cancer cells. Our results indicated that I3C inhibited the proliferation of OVCAR-3 cells, a process which was associated with inhibition of cell motility as determined by wound healing experiments and cell invasion studies. I3C treatment increased the tightness of the tight junctions (TJs), which was demonstrated by an increase in transepithelial electrical resistance and a decrease in paracellular permeability. The RT-PCR and immunoblotting results indicated that I3C repressed the levels of claudin-3 as well as claudin-4, proteins that comprise a major part of TJs and play a key role in the control and selectivity of paracellular transport. Furthermore, the activities of matrix metalloproteinase (MMP)-2 and MMP-9 were also decreased by treatment with I3C, which was connected with the down-regulation of their mRNAs and protein expression. The results suggest that I3C may be expected to inhibit cancer cell metastasis and invasion by restoring TJs and decreasing MMP activity in ovarian cancer cell line OVCAR-3.

The Effects of Glucagon-like Peptide-2 on the Tight Junction and Barrier Function in IPEC-J2 Cells through Phosphatidylinositol 3-kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling Pathway

  • Yu, Changsong;Jia, Gang;Deng, Qiuhong;Zhao, Hua;Chen, Xiaoling;Liu, Guangmang;Wang, Kangning
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.5
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    • pp.731-738
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    • 2016
  • Glucagon-like peptide-2 (GLP-2) is important for intestinal barrier function and regulation of tight junction (TJ) proteins, but the intracellular mechanisms of action remain undefined. The purpose of this research was to determine the protective effect of GLP-2 mediated TJ and transepithelial electrical resistance (TER) in lipopolysaccharide (LPS) stressed IPEC-J2 cells and to test the hypothesis that GLP-2 regulate TJ and TER through the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway in IPEC-J2 cells. Wortmannin and LY294002 are specific inhibitors of PI3K. The results showed that $100{\mu}g/mL$ LPS stress decreased TER and TJ proteins occludin, claudin-1 and zonula occludens protein 1 (ZO-1) mRNA, proteins expressions (p<0.01) respectively. GLP-2 (100 nmol/L) promote TER and TJ proteins occludin, claudin-1, and zo-1 mRNA, proteins expressions in LPS stressed and normal IPEC-J2 cells (p<0.01) respectively. In normal cells, both wortmannin and LY294002, PI3K inhibitors, prevented the mRNA and protein expressions of Akt and mTOR increase induced by GLP-2 (p<0.01) following with the significant decreasing of occludin, claudin-1, ZO-1 mRNA and proteins expressions and TER (p<0.01). In conclusion, these results indicated that GLP-2 can promote TJ's expression and TER in LPS stressed and normal IPEC-J2 cells and GLP-2 could regulate TJ and TER through the PI3K/Akt/mTOR pathway.

The Effect of Treadmill Exercise and Environmental Enrichment on Cognitive Function, Muscle Function, and Levels of tight junction protein in an Alzheimer's Disease Animal Model (트레드밀 운동 및 환경강화가 알츠하이머 질환 동물 모델의 인지기능, 근 기능 및 밀착연접 단백질 수준에 미치는 영향)

  • Hyun-Seob Um;Jong-Hwan Jung;Tae-Kyung Kim;Yoo-Joung Jeon;Joon-Yong Cho;Jung-Hoon Koo
    • Journal of the Korean Applied Science and Technology
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    • v.41 no.1
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    • pp.58-68
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    • 2024
  • The purpose of this study was to investigate the effects of treadmill exercise treadmill exercise (TE) and environmental enrichment (EE) interventions on cognitive function, muscle function, and the expression of tight junction proteins in an Alzheimer's disease (AD) animal model. To create the AD animal model, aluminum chloride (AlCl3) was administered for 90 days (40mg/kg/day), while simultaneously exposing the animals to TE (10-12m/min, 40-60min/day) or EE. The results showed that cognitive impairment and muscle dysfunction induced by AlCl3 administration were alleviated by TE and EE. Furthermore, TE and EE reduced the increased expression of β-amyloid(Aβ), alpha-synuclein, and tumor necrosis factor-α (TNF-α) proteins observed in AD pathology. Additionally, TE and EE significantly increased the expression of decreased adhesive adjacent proteins (Occludin, Claudin-5, and ZO-1) induced by AlCl3 administration. Lastly, correlation analysis between Aβ protein and tight junction proteins showed negative correlations (Occludin: r=-0.853, p=0.001; Claudin-5: r=-0.352, p=0.915; ZO-1: r=-0.424, p=0.0390). In conclusion, TE or EE interventions are considered effective exercise methods that partially alleviate pathological features of AD, improving cognitive and muscle function.

Inhibitory Effect of Steviol and Its Derivatives on Cell Migration via Regulation of Tight Junction-related Protein Claudin 8 (스테비올 및 그 유도체의 세포연접 관련 클라우딘 8 발현 조절을 통한 세포이동 저해효과)

  • Choi, Sun Kyung;Cho, Nam Joon;Cho, Uk Min;Shim, Joong Hyun;Kim, Kee K.;Hwang, Hyung Seo
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.4
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    • pp.403-412
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    • 2016
  • The tight junction, one of Intercellular junctions, performs a variety of biological functions by bonding adjacent cells, including the barrier function to control the movement of the electrolyte and water. Recent studies have revealed that unusual expression of tight junction-related genes have been shown to be related in cancer development and progression. Recently, there are many reports that control of tight junction proteins expression is closely related to the skin moisture. In this study, we are focusing on the regulating mechanism of tight junction-associated genes by the steviol and its derivatives. Steviol, used as a sweetner, is known to chemical compound isolated from stevia plant. The MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) assay was carried out in HaCaT cells (human keratinocyte cell line) in order to determine the cytotoxicity. As a result, while steviol showing cytotoxicity from $250{\mu}M$, steviol derivatives are not cytotoxic more than $250{\mu}M$ concentration. We have observed a change in the tight junction protein via quantitative real-time PCR. Claudin 8 among tight junction proteins is only significantly reduced up to 30% in the presence of steviol. In addition, cell migration was inhibited by steviol, not by stevioside and rebaudioside. Finally, we could observe that steviol, not stevioside and rebaudioside, is able to increase the skin barrier permeability through the transepithelial electric resistance (TEER) measurements. These results suggest that the steviol and its derivatives are specifically acts on the tight junction related gene expression, but steviol derivatives are more suitable as a cosmetic material.

Effects of Oral Administered Hot Water Extracts of Korean Black Ginseng on Wound Healing in Mice (피부(皮膚) 창상(創傷) 동물모델에서 흑삼(黑蔘) 열수 추출물 경구 투여의 효과)

  • Kim, Tae-Ryeong;Kim, Young-Jun;Woo, Chang-Hoon
    • Journal of Korean Medicine Rehabilitation
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    • v.32 no.1
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    • pp.1-19
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    • 2022
  • Objectives This study aims to evaluate the wound healing effects of oral administered hot water extracts of Korean black ginseng (KBG). Methods 40 C57BL/6 mice were divided into five groups; normal, control, vitamin E 200 mg/kg, KBG 100 mg/kg, KBG 200 mg/kg, each n=8. Skin wounds were made in the back of all mice except normal group using biopsy punches. Wounds were observed on days 7 and 14 after injury. The anti-oxidant and inflammatory protein levels were evaluated using western blotting. Skin tissue was analyzed by hematoxylin & eosin and Masson's trichrome staining method. Results KBG significantly accelerated reducing wound area. KBG significantly decreased myeloperoxidase activity. KBG significantly decreased oxidative stress factors such as NADPH oxidase-4 and p22phox and increased antioxidant enzymes including nuclear factor erythroid 2-related factor2, kelch-like ECH-associated protein-1, heme oxygenase-1, superoxide dismutase, catalase and glutathione peroxidase-1/2. Moreover, KBG significantly decreased inflammation factors including nuclear factor-κB, phosphorylated inhibitor of κBα, cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α and interleukin (IL)-6 and increased anti-inflammation cytokine such as IL-4 and IL-10. In addition, KBG significantly increased tight junction proteins including claudin-1, claudin-3, claudin-4. In histopathologic, KBG made the epithelium thin and uniform, and accelerated the remodeling of collagen. Conclusions The results suggest that KBG has healing effects on skin wound in mice by anti-inflammatory and antioxidant activity.

Effect of Intestinal Tight Junction Protein Expression on Growth Performance for Eco-friendly Broiler Production: Meta-analysis (친환경 육계 생산을 위한 장 점막 밀접 접합 단백질의 발현량 조절이 생산성에 미치는 효과: Meta-analysis)

  • Jeon, Eun-Jeong;Park, Myung-Sun;Han, Jae-Kyu;Kim, Joung-Yong;Ahn, Sung-Il
    • Korean Journal of Organic Agriculture
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    • v.29 no.1
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    • pp.125-136
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    • 2021
  • In this study, a meta-analysis was performed to determine the correlation between the expression of tight junction protein in the intestine and the productivity of broiler chickens. A total of 9 papers were selected in which the result values consisted of the mean and standard deviation value, and the standardized mean difference was calculated to compare the mean of the control and treatment groups. A meta-regression test was conducted to determine the effect of each type of tight junction protein. The TJPs observed in each study were claudin1, claudin2, claudin3, occludin, ZO1, ZO2, etc., and the indicators to indicate the productivity of broilers were body weight gain (BWG), feed intake (FI), and feed conversion rate (FCR), average daily feed intake (ADFI), average daily gain (ADG), and feed/gain ratio (FPG). Although there are differences depending on the type of TJP, it was found that the change in expression level had a close effect on the productivity of broilers. In particular, occludin significantly correlated with body weight gain, feed intake, and feed conversion rate. Based on the results of this study, a study on a method to effectively increase the expression level of TJP is expected to contribute to improving the productivity of broilers and producing safe livestock products.