• Title/Summary/Keyword: Claudin-3

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Expression Pattern and Prognostic Significance of Claudin 1, 4 and 7 in Pancreatic Cancer

  • Alikanoglu, Arsenal Sezgin;Gunduz, Seyda;Demirpence, Ozlem;Suren, Dinc;Gunduz, Umut Riza;Sezer, Cem;Yildiz, Mustafa;Yildirim, Mustafa
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4387-4392
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    • 2015
  • Background: Tight junctions (TJs) organise paracellular permeability and they have an important role in epithelial and endothelial cell polarity and permanence of barrier function. It has been demonstrated that the Claudin family constitutes an important component of them. In this study, we assessed expression patterns of of Claudin1, 4 and 7 and whether they have any relation with prognosis in patients with pancreatic cancer. Materials and Methods: Expression patterns of Claudin 1,4 and 7 were examined by immunohistochemistry in 25 patients with a histopathological diagnosis of pancreatic cancer using a semiquantitative scoring of the extent and intensity of staining. After grouping the staining scores as low (final score 0-2) and high (final score 3-9) the relation between expression of Claudin 1,4 and 7 and survival was evaluated. Results: There was no significant relation between expression of Claudin 1,4 and 7 and gender and stage. No statistically significant relation was found between Claudin 1 and 4 expression and survival whereas a statistically significant relation was found between decrease in Claudin 7 expression and decrease in survival. Conclusions: Claudins have important functions other than their popular function known as adhesion. Supporting this hypothesis, we found a statistically significant relationship between increased Claudin 7 expression and increased survival time, and this suggests that Claudin 7 may exert different tumorigenic effects in pancreatic cancer other than its well-known adhesion effect.

Indol-3-Carbinol Regulated Tight Junction Permeability and Associated-Protein Level and Suppressed Cell Invasion in Human Colon Cancer Cell Line, HT-29 (인돌 (Indol-3-Carbinol)이 인체대장암세포 HT-29 세포의 투과성 밀착결합조절과 세포 침윤성 억제에 미치는 영향)

  • Kim, Sung-Ok;Choi, Yung-Hyun;Choe, Won-Kyung
    • Journal of Nutrition and Health
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    • v.41 no.1
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    • pp.13-21
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    • 2008
  • To determine whether indol-3-carbinol (BC, $C_9H_9NO$), an autolysis product of a glucosinolate and a glucobrassicin in vegetables, regulated tight junction proteins (TJ) and suppressed cell invasion in colon cancer cells, this experiment was performed. Our results indicate that I3C inhibit cell growth of HT-29 cells in a dose (0, 50, $100{\mu}M$) and time (0, 24 and 48h) dependent manner. Using the wound healing and matrigel invasion study, respectively, BC inhibits the cell motility and invasion of the ovarian cancer cell line. The TEER values were increased in HT-29 cells grown in transwells treated with BC, reversely, paracellular permeability was decreased in those of condition. Claudin-1, claudin-5, ZO-1 and occuldin have been shown to be positively expressed in HT-29 coloncancer cells. I3C occurs concurrently with a significant decrease in the levels of those of proteins in HT-29 cells. But E-cadherin level in the HT-29 was increased by I3C. The reduction of claudin-1 and claudin-5 protein levels occurred post-transcriptionaly since their mRNA levels are no difference by I3C. Therefore, our results suggest that I3C may be expected to inhibit cancer metastasis and invasion by tighten the cell junction and restoring tight junction in colon cancer cell line, HT-29.

Prognostic Significance of Claudin 4 in Completely Resected Adenocarcinoma of the Lung

  • Chae, Min Cheol;Park, Chang Kwon;Keum, Dong Yoon;Hwang, Ilseon;Kwon, Kun Young;Jang, Byeong Churl
    • Journal of Chest Surgery
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    • v.47 no.3
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    • pp.262-268
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    • 2014
  • Background: The development of diagnostic techniques and an awareness of health examinations can bring about an early diagnosis of lung cancer. However, appropriate postoperative management and adjuvant chemotherapy remain under debate in postoperative therapeutic strategy. The present study was conducted to assess the clinicopathologic factors that influence recurrence and prognosis after complete resection of lung cancer. Methods: The present study analyzed 62 patients with lung cancer who underwent complete resection of diagnosed adenocarcinoma between 1994 and 2007. In addition to conventional factors, which include staging factor and histological evaluation, the present study also performed univariate and multivariate analyses to consider claudin, a cell adhesion molecule, as a prognostic factor by immunohistochemical staining. Results: There was no correlation between conventional factors, including lymphatic and vascular invasion, and recurrence. However, there was a significant correlation between high expression of claudin 4 and cancer recurrence. In particular, there was a correlation between high expressions of claudin 1, 4, and 5 and a reduction of disease-free survival. Conclusion: Increased expressions of claudin 4 were negative prognostic factors in adenocarcinoma of the lung and thus could be used to identify high-risk patients for adjuvant chemotherapy, even if they had early-stage lung cancer. The present findings collectively suggest that consideration of claudin as a prognostic factor in the active postoperative treatment in patients at high risk will lead to better therapeutic outcomes with fewer side effects.

Anti-invasive Activity of Human Breast Carcinoma Cells by Genistein through Modulation of Tight Junction Function (인체유방암세포의 tight junction 기능 조절을 통한 genistein의 암세포 침윤 억제 효과)

  • Kim, Sung-Ok;Jeang, Yang-Kee;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.9
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    • pp.1200-1208
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    • 2009
  • Tight junctions (TJs) that act as paracellular permeability barriers play an essential role in regulating the diffusion of fluid, electrolytes and macromolecules through the paracellular pathway. In this study, we investigated the correlation between the tightening of TJs, permeability and the invasive activity of genistein - a bioactive isoflavone of soybeans - in human breast carcinoma MCF-7 and MDA-MB-231 cells. The inhibitory effects of genistein on cell proliferation, motility and invasiveness were found to be associated with the increased tightness of the TJs, which was demonstrated by an increase in transepithelial electrical resistance and a decrease in paracellular permeability. Additionally, the immunoblotting results indicated that genistein repressed the levels of the proteins that comprise the major components of TJ, claudin-3 and claudin-4, which play a key role in the control and selectivity of paracellular transport. Furthermore, genistein decreased the metastasis-related gene expressions of insulin like growth factor-1 receptor and snail, while concurrently increasing that of thrombospondin-1 and E-cadherin. In addition, we demonstrated that claudins play an important role in the anti-motility and invasiveness of genistein using claudin-3 small interfering RNA. Taken together, our results indicate a possible role for genistein as an inhibitor of cancer cell invasion through the tightening of TJs, which may counteract the up-regulation of claudins. In addition, our results indicate that this may be beneficial for the inhibition of tumor metastasis.

The Expression and Localization of ZO-1, Claudin 1, and Claudin 4 in the Pig Epididymis (돼지 정소상체에서 ZO-1, Claudin 1 및 Claudin 4의 발현 양상)

  • Park, Yun-Jae;Kim, Bongki
    • Journal of Animal Reproduction and Biotechnology
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    • v.34 no.3
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    • pp.190-196
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    • 2019
  • Tight junctions are constituents of the blood-epididymis barrier that play roles in regulating the unidirectional transcellular transport of ions, water, and solutes to maintain optimal conditions for sperm maturation and storage. Claudin 1 (Cldn1) and 4 (Cldn4) are known as tight junction proteins and are expressed in the basolateral membranes as well as tight junctions in the epididymis of rodents. Here, we examined the expression and localization of Cldn1 and 4 to determine the function of these proteins in the pig epididymis. Cldn1 was highly expressed in the basolateral membrane of epithelial cells in the caput and corpus regions of the epididymis. In the cauda region, however, Cldn1 labeling was significantly decreased in the basolateral membrane of epithelial cells. In contrast, labeling indicated that Cldn4 was expressed in the basolateral membrane in the cauda region of the epididymis and was present at punctate reactive sites in the caput and corpus regions. However, in no region of the epididymis did we detect colocalization of Cldn1 and 4 with labeled ZO-1, the distribution of which is restricted to the tight junctions. Our results indicate that Cldn1 and 4 were region-specifically expressed in the pig epididymis but not present in the tight junctions of epididymal epithelium. In addition, reciprocal regulation in specific regions of the epididymis between Cldn1 and 4 may play an important role in generating an optimal luminal environment for sperm maturation and storage in the pig epididymis.

Anti-invasive activity of histone deacetylase inhibitors via the induction of Egr-1 and the modulation of tight junction-related proteins in human hepatocarcinoma cells

  • Kim, Sung-Ok;Choi, Byung-Tae;Choi, Il-Whan;Cheong, Jae-Hun;Kim, Gi-Young;Kwon, Taeg-Kyu;Kim, Nam-Deuk;Choi, Yung-Hyun
    • BMB Reports
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    • v.42 no.10
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    • pp.655-660
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    • 2009
  • The potential anti-metastasis and anti-invasion activities of early growth response gene-1 (Egr-1) and claudin-3, a tight junction (TJ)-related protein, were evaluated using histone deacetylase (HDAC) inhibitors in human hepatocarcinoma cells. The results of wound healing and Transwell assays showed that HDAC inhibitors such as trichostatin A and sodium butyrate inhibited cell migration and invasion. HDAC inhibitors markedly induced Egr-1 expression during the early period, after which expression levels decreased. In addition, the down-regulation of snail and type 1 insulin-like growth factor receptor (IGF-1R) in HDAC inhibitor- treated cells induced the upregulation of thrombospondin-1 (TSP-1), E-cadherin and claudin-3. Cells transfected with Egr-1 and claudin-3 siRNA displayed significant blockage of HDAC inhibitor-induced anti-invasive activity. Collectively, these findings indicate that the up-regulation of Egr-1 and claudin-3 are crucial steps in HDAC inhibitor-induced anti-metastasis and anti-invasion.

Effects of 3,3′,4,4′,5-pentachloro biphenyl (PCB126) on the Expression the Tight Junction Genes in Cultured Mouse Neonatal Testis

  • Gye, Myeong-Chan;Fukuzawa, Noriho Honda;Ohsako, Seiichiro
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.63-63
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    • 2003
  • In an effort to uncover the spermatogenic impairment by the polychlorinated biphenyls (PCBs), the expression of tight junctions (TJs) genes important for the formation of the blood testis barrier (BTB) were examined following the 3,3',4,4',5-pentachloro biphenyl (PCB126) treatment in cultured neonatal testis in mice. At 4 days (D4) after 10 and 100 nM PCB126 treatment the expression of claudin-11 was significantly increased when compared with vehicle control. In contrast no difference in occludin and claudin-1 expression was found among the experimental group. On D8, 100 nM PCB126 significantly increased the expression of claudin-11 but not occludin and claudin-1. 1 uM PCB126 treatment significantly decreased expressions of occludin and ciaudin -1, suggesting the general toxic effect on the Sertoli cell. Because PCB126 does not alter the proliferative activity of spermatogenic cells and Sertoli cells in neonatal testis, it is likely that increase in the expression of claudin-11 by low dose of PCB126 may attribute to the alteration of the Sertoli cells differentiation in testis. It also emphasized that PCB126 might have differentially affected the transcription of TJ genes in Sertoli cells. In conclusion, this result suggests that the structure of TJ may be targeted by PCB126 in neonatal testis in mice and that co-PCB is potentially harmful to spermatogenesis by alteration of the development of BTB.

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Novel Sporichthyaceae Bacterium Strain K-07 Skin Barrier, Moisturizing and Anti-inflammatory Activity (신규 Sporichthyaceae Bacterium Strain K-07 배양액의 피부장벽, 보습 및 항염증 활성)

  • Lee, Dong-Geol;Kim, Minji;Kang, Seunghyun;Kim, Youn-Joon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.43 no.2
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    • pp.137-147
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    • 2017
  • The human skin is an ecosystem that provides habitat to various microorganisms. These comprise the skin microbiome and provide numerous benefits in addition to maintaining a symbiotic relation with the host. Various metabolites generated by the skin microbiome exert beneficial effects such as strengthening the skin barrier, and anti-aging and anti-inflammatory functions. In this study, we isolated a novel bacterium, designated Sporichthyacae strain K-07, from the human skin. Analysis of 16S rRNA gene sequences showed that the newly found bacterium shares 93.4% homology with the genus Sporichthya, thus corroborating the discovery of a novel genus. We further analyzed the effect of the novel strain in vitro, by treating HaCaT cells with bacterial metabolite products. Treatment resulted in changes in the mRNA expression levels of filaggrin, claudin1, claudin4, SMase, CERS3, HAS3, aquaporin3, IL-6, TNF-${\alpha}$, TSLP, and TARC. Specifically, the levels of filaggrin, claudin1, claudin4, SMase, CERS3, HAS3, and aquaporin3 were higher in strain K-07 metabolite product-treated cells than in control cells. These results showed that metabolite products of the novel strain K-07 enhanced the skin barrier and exert anti-inflammatory effects. Therefore, these metabolite products could be potentially used for treatment of skin conditions.

(β-lapachone Regulates Tight Junction Proteins, Claudin-3 and -4, in Human Hepatocarcinoma Cells. (인체 간암세포에서 β-lapachone 처리에 의한 Tight Junction 관련 유전자의 변화)

  • Kim, Sung-Ok;Kwon, Jae-Im;Kim, Gi-Young;Kim, Nam-Deuk;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.17 no.9 s.89
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    • pp.1298-1302
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    • 2007
  • A hallmark of cancers is 'leaky' tight junctions (Tjs). TJs mediated paracellular permeability is elevated and TJs maintained cell polarity is frequently lost. Concomitantly, TJs-associated proteins including members of the claudin family of proteins are dysregulated. Recent findings indicate that these TJs changes can contribute to cancer progression. In this study, we examined the effects of ${\beta}-lapachone$, a quinone compound obtained from the bark of the lapacho tree (Tabebuia avellanedae), on the Tjs-associated regulators in human hepatocarcinoma cell lines, HepG2 and Hep3B. ${\beta}-lapachone$ treatment downregulated the levels of insulin-like growth factor 1 receptor (IGF-lR) proteins in both HepG2 and Hep3B cells. But the levels of claudin-3 and -4 proteins were increased in ${\beta}-lapachone$-treated HepG2 and Hep3B cells. And also the zonnula occludens-l (la-I) and p-catenin protein levels by ${\beta}-lapachone$ were increased in a time-dependent manner. However, claudin-3 and -4 mRNA levels were uninhibited by ${\beta}-lapachone$ in HepG2 and Hep3B. The present results suggest that the upregulation of claudin-3 and -4 protein levels by ${\beta}-lapachone$ occurs by a post-transcriptional mechanism and points to a novel mechanism by ${\beta}-lapachone$.

Investigation of the effect of Lithospermi Radix on tight-junction related genes in HaCaT cells (자초(紫草) 열수추출물이 각질형성세포 HaCaT의 세포 연접 관련 유전자의 발현에 미치는 영향 연구)

  • Cho, Namjoon;Lee, Byeongkwon;Lee, Woonghee;Kim, Keekwang;Kim, Kyoon Eon;Han, Hyosang
    • The Korea Journal of Herbology
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    • v.32 no.3
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    • pp.55-61
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    • 2017
  • Objectives : The aim of this research was to determine the diverse effects of Lithospermi Radix Water Extract (LR) on human keratinocyte HaCaT cells, and to examine whether those effects could be applied to the human skin. Methods : We examined effect of LR on the cell viability of using the MTS assay in human keratinocyte HaCaT cells. The antioxidation effect of LR was analyzed relative to the well-known antioxidant resveratrol, using an ABTS assay. Quantitative RT-PCR analysis revealed that, in HaCaT cells, LR influenced the mRNA expression of tight-junction genes associated with skin moisturization. Furthermore, a wound-healing assay demonstrated altered cell migration in LR-treated HaCaT cells. Result : The cytotoxicity was confirmed to be higher in LR at a concentration of $800{\mu}g/m{\ell}$ using the MTS assay in HaCaT cells. In comparison to $100{\mu}M$ resveratrol, $1,600{\mu}g/m{\ell}$ LR showed either a similar or superior antioxidation effect. LR treatment in HaCaT cells reduced the mRNA expression levels of claudin 3, claudin 4, claudin 6, claudin 8, and ZO-2 to less than 0.80-fold, whereas JAM-A and Tricellulin mRNA expression level increased more than 1.33-fold. In addition, HaCaT cells migration was decreased to 83.9% by LR treatment. Conclusions : LR of antioxidation activity will have an anti-aging effect on the skin by reducing oxidative stress. Further studies are required to address the implications for human skin, given LR's effects of altering mRNA expression of tight junction-related gene and decreasing cell migration of HaCaT cells.