Comparison of Tight Junction Protein-Related Gene mRNA Expression Levels between Male and Female Gastroesophageal Reflux Disease Patients

BACKGROUND/AIMS: Male predominance has been observed in the erosive reflux disease (ERD), but reverse finding in nonerosive reflux disease (NERD). This suggests sex-specific medicine approach is needed but its mechanism is remained to be elucidated. We aimed to compare clinical characteristics and mRNA expression levels of tight junction-related proteins between male and female gastroesophageal reflux disease (GERD). METHODS: Sixteen healthy controls, 45 ERD, and 14 NERD patients received upper endoscopies and completed questionnaires. Quantitative real-time polymerase chain reactions of occludin (OCLN), zonal occludens (ZO) 1, claudin-1 (CLDN1) and claudin-4 (CLDN4), and neurokinin 1 receptor (NK1R) were performed in the distal esophageal mucosal specimen. These results were analyzed by sex. RESULTS: Female GERD patients were affected more by reflux symptoms than males. The impairment of overall quality of life was more prominent in female patients with reflux symptoms than male patients (5.6±0.2 vs 4.9±0.6, p=0.009). The levels of OCLN mRNA expression were significantly lower in the male ERD group. On the other hand, those of CLDN1, CLDN4, and NK1R except ZO-1 were significantly higher in the male ERD group. CONCLUSIONS: We demonstrated that female ERD/NERD patients were affected more by GERD and male ERD patients showed significant changes of tight junction protein mRNA expression levels.

Effects of 17β-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model

BACKGROUND/AIMS: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. METHODS: The effects of 17β-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. RESULTS: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p < 0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-κB, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. CONCLUSIONS: E2 acts through the estrogen receptor β signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.

Value of combined detection of claudin 4 and high-risk human papilloma virus in high-grade squamous intraepithelial lesion and cervix squamous cell carcinoma / 浙江大学学报·医学版

OBJECTIVE@#To investigate the expression of claudin 4 (CLDN4) in cervical tissues from patients with different cervical lesions, and to explore the value of combined detection of CLDN4 and high risk human papilloma virus (HR-HPV).@*METHODS@#The cervical tissue specimens of low-grade squamous intraepithelial lesion (LSIL, =30), high-grade squamous intraepithelial lesion (HSIL, =30), squamous cell carcinoma (SCC, =30) as well as chronic cervicitis (control, =30) were collected from the Sir Run Run Shaw Hospital of Zhejiang University during June 2015 and December 2016. The expression of CLDN4 protein in tissue specimens was detected by immunohistochemistry, HR-HPV was detected by real-time quantitative PCR, and the cervical exfoliated cells were examined by thinprep cytologic test (TCT). The ROC curve was applied to analyze the diagnostic value of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for HSIL and SCC of the cervix.@*RESULTS@#With the increase of the severity of cervical lesions, the positive rate of CLDN4 expression rose (=0.832, <0.05). Positivity of both HR-HPV infection and CLDN4 expression was found mainly in the HSIL and SCC groups. The areas under curve (AUC) of TCT combined with HR-HPV and CLDN4 combined with HR-HPV tests for diagnosis of HSIL and SCC were 0.683 and 0.633, respectively; the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of TCT combined with HR-HPV test for diagnosis of HSIL and SCC were 100.0%, 36.7%, 61.2%, 100.0% and 46.7% respectively; those of CLDN4 combined with HR-HPV test were 96.7%, 30.0%, 58.0%, 90.0% and 55.0%, respectively.@*CONCLUSIONS@#CLDN4 expression may be related to the occurrence and development of cervical carcinoma and precancerous lesions. CLDN4 combined with HR-HPV test may be used for diagnosis of HSIL and SCC of the cervix clinically.

Alteration in Claudin-4 Contributes to Airway Inflammation and Responsiveness in Asthma

PURPOSE: Claudin-4 has been reported to function as a paracellular sodium barrier and is one of the 3 major claudins expressed in lung alveolar epithelial cells. However, the possible role of claudin-4 in bronchial asthma has not yet been fully studied. In this study, we aimed to elucidate the role of claudin-4 in the pathogenesis of bronchial asthma. METHODS: We determined claudin-4 levels in blood from asthmatic patients. Moreover, using mice sensitized and challenged with OVA, as well as sensitized and challenged with saline, we investigated whether claudin-4 is involved in the pathogenesis of bronchial asthma. Der p1 induced the inflammatory cytokines in NHBE cells. RESULTS: We found that claudin-4 in blood from asthmatic patients was increased compared with that from healthy control subjects. Plasma claudin-4 levels were significantly higher in exacerbated patients than in control patients with bronchial asthma. The plasma claudin-4 level was correlated with eosinophils, total IgE, FEV1% pred, and FEV1/FVC. Moreover, lung tissues from the OVA-OVA mice showed significant increases in transcripts and proteins of claudin-4 as well as in TJ breaks and the densities of claudin-4 staining. When claudin-4 was knocked down by transfecting its siRNA, inflammatory cytokine expressions, which were induced by Der p1 treatment, were significantly increased. CONCLUSIONS: These findings thus raise the possibility that regulation of lung epithelial barrier proteins may constitute a therapeutic approach for asthma.

Claudin-1, -2, -4, and -5: comparison of expression levels and distribution in equine tissues

Claudins, which are known as transmembrane proteins play an essential role in tight junctions (TJs) to form physical barriers and regulate paracellular transportation. To understand equine diseases, it is helpful to measure the tissue-specific expression of TJs in horses. Major equine diseases such as colic and West Nile cause damage to TJs. In this study, the expression level and distribution of claudin-1, -2, -4, and -5 in eight tissues were assessed by Western blotting and immunohistochemistry methods. Claudin-1 was primarily identified in the lung, duodenum, and uterus, claudin-2 was evenly observed in equine tissues, claudin-4 was abundantly detected in the liver, kidney and uterus, and claudin-5 was strongly expressed in the lung, duodenum, ovary, and uterus, as determined by Western blotting method. The localization of equine claudins was observed by immunohistochemistry methods. These findings provide knowledge regarding the expression patterns and localization of equine claudins, as well as valuable information to understand tight junction-related diseases according to tissue specificity and function of claudins in horses.

Tight junction protein claudin 4 in gastric carcinoma and its relation to lymphangiogenic activity

Background and study aims: Gastric cancer is the second most common cause of cancer-related death worldwide. Claudins are a family of tight junction proteins that are biologically relevant in many cancer progression steps. This study aimed to investigate the expression of the intestinal claudin [claudin 4] in gastric carcinoma and to evaluate its relation to the different clinicopathologic prognostic parameters, especially lymphangiogenesis [production of new lymphatic vessels, measured by lymphovascular density [LVD]] and lymphovascular invasion [LVI]

Patients and methods: Fifty-five gastric carcinoma specimens were immunohistochemically stained for claudin 4 and D2-40 [for detection of lymphatic vessel endothelium]

Results: High expression of claudin 4 was detected in 26 of 55 [47.3%] cases. Low expression of claudin 4 was related to poorly differentiated type [p = 0.001], non-intestinal [diffuse] type [p = 0.001], deeper tumour invasion [p < 0.001], lymph node metastasis [p = 0.001], and higher stage [p = 0.001]. In addition, higher LVD was related to poorly differentiated types [p = 0.001], non-intestinal type [p = 0.001], lymph node metastasis [p = 0.015], and higher tumour, node, metastasis [TNM] stage [p = 0.001]. LVI was related to lymph node metastasis [p = 0.025], higher TNM stage [p = 0.001], and LVD [p = 0.001]. Claudin 4 significantly correlated with both LVD [p = 0.009] and LVI [p = 0.009]

Conclusions: High expression of claudin 4 was associated with the more differentiated intestinal-type gastric carcinoma and lost in poorly differentiated diffuse type. So, claudin 4 may be used as one of the differentiating markers between the two major types of gastric carcinoma [intestinal vs. diffuse]. LVD and LVI were related to higher incidence of lymph node metastasis and therefore could be used as predictive markers for lymph node metastasis in limited specimens during early gastric carcinoma to determine the need for more invasive surgery. Low expression of claudin 4 was related to lymphangiogenesis. This may shed light on the relation of tight junction protein expression and lymphangiogenesis

Tight junction protein expression of gastric mucosa and its significance in children with Helicobacter pylori infection / 中华儿科杂志

<p><b>OBJECTIVE</b>To understand the junction protein expression of gastric mucosa including occlusal proteins (occludin), closed protein-4 (claudin-4), zonula occluden-1(ZO-1), epithelial cadherin (E-cadherin), and β ring protein (β-catenin) and the clinical significance in children with Helicobacter pylori (Hp) infection.</p><p><b>METHOD</b>Seventy patients in whom gastric endoscopy was performed because of nausea, vomiting, abdominal pain, bloating, acid reflux, melena, and other gastrointestinal symptoms were enrolled in this study from Dec. 2010 to Apr. 2013 in our hospital. Informed consent was signed by their parents, and the study was in accordance with the principles of medical ethics. Hp positivity was confirmed if both respiratory urea test (RUT) and Hp were positive by gastric mucosal pathology. Gastric mucosal samples from 70 patients were enrolled in this study, 23 of them were Hp negative, 47 of them were Hp positive (24 cases without peptic ulcer, 23 cases with peptic ulcer). The mRNA levels and protein expression of tight junction protein of gastric mucosa were measured by RT-PCR and Western blot respectively. The location and semi quantitative content of E-cadherin and β-catenin in gastric mucosa were detected by immunohistochemical staining method.</p><p><b>RESULT</b>The mRNA level of E-cadherin, β-catenin, ZO-1 in the Hp positive group regardless of peptic ulcer was significantly lower than that in the Hp negative group. Hp positive without peptic ulcer group were 0.0008, 0.0040, 0.0014, respectively; Hp positive with peptic ulcer group were 0.0010, 0.0090, 0.0013, respectively; Hp negative group were 0.0137, 0.0423, 0.0198, respectively (F values were 36.956, 39.893, 38.962, respectively, all P<0.05). The expression of claudin-4 mRNA in Hp positive group with peptic ulcer increased significantly, the difference among Hp positive group with peptic ulcer, Hp positive group without peptic ulcer and Hp negative group was statistically significant (0.1438 vs. 0.0926 vs. 0.0789) (F value was 11.964, P<0.05), while the difference of occludin mRNA levels among the three groups was not statistically significant.Immunohistochemistry results showed that the score of E-cadherin, β-catenin positive cell in the Hp positive patients were also significantly lower than that in the Hp negative group (t values were 3.981 and 2.340, all P<0.05, respectively). Western blot results showed that the protein levels of β-catenin in Hp positive group with peptic ulcer were significantly lower than that in Hp negative group, while the protein levels of E-cadherin in Hp positive patients regardless of peptic ulcer were decreased significantly in Hp negative group.</p><p><b>CONCLUSION</b>Our results revealed that the tight junction protein E-cadherin, β-catenin, ZO-1 expression of gastric mucosa were decreased in children with Hp infection, while claudin-4 expression was increased in Hp positive patients with peptic ulcer, suggesting that damage to gastric epithelial barrier function may be the main pathogenesis of Hp associated gastric diseases in children.</p>

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

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.

Acute Modulations in Stratum Corneum Permeability Barrier Function Affect Claudin Expression and Epidermal Tight Junction Function via Changes of Epidermal Calcium Gradient

Tight junction (TJ) is recognized as a second barrier of the skin. Altered expression of TJ proteins in various skin diseases characterized by the abnormal permeability barrier such as psoriasis suggests that TJ could be affected by stratum corneum (SC) barrier status. However, the physiological relationship between SC and TJ barrier remains to be investigated. Therefore, we examined the effect of SC barrier disruption on the expression of TJ proteins, claudin (Cldn)-1 and Cldn-4, and TJ barrier function in hairless mouse skin. We also investigated whether the alterations in epidermal Ca2+ affected TJ proteins expression in vivo. Repeated tape-stripping induced a sequential change of the expression and function of TJ. As early as 15-30 minutes after tape-stripping, downregulation of Cldn-1 and Cldn-4 immunoreactivity and protein level without change in mRNA level was found. This was accompanied by the abnormal leakage of lanthanum. However, by 1 hour Cldn-1 and Cldn-4 immunolocalization recovered along with normalized lanthanum permeation pattern. Moreover, the mRNA and protein levels of Cldn-1 and Cldn-4 were increased by 1 to 6 hours after tape-stripping. Inhibition of calcium loss by immersion of barrier-disrupted skin into a high Ca2+ solution prevented the dislocation of Cldn-1 and Cldn-4. Occlusion of barrier-disrupted skin delayed the restoration of Cldn-1 and Cldn-4. Our results suggest that the alteration of epidermal Ca2+ gradient caused by SC barrier perturbation affects the TJ structure and function and the faster recovery of TJ as compared to the SC barrier may imply the protective homeostatic mechanism of skin barrier.

Screening of membrane antigen differentially expressed in androgen-dependent prostate cancer and androgen-independent prostate cancer / 中南大学学报(医学版)

OBJECTIVE@#To determine the screening of the expression of membrane proteins in androgen-dependent prostate cancer (ADPC) and androgen-independent prostate cancer (AIPC) and to explore the mechanism of membrane proteins in these two cancers.@*METHODS@#Serum samples were collected from 3 patients with ADPC and another 3 patients with AIPC. The serum was incubated with ADPC cell line LNCaP and/or AIPC cell line PC-3 and detected by immunoprecipitation and Western blot. Differentially expressed proteins between ADPC and AIPC identified by mass spectrometry were compared and their expression level and location were analyzed by immunofluorescence.@*RESULTS@#Altogether 11 membrane proteins were identifited, such as the Neural-Cadherin precursor, ER60 precursor, Claudin-4, and so on. Immunofluorescence revealed that the expression level of Claudin-4 in PC-3 cells was higher than in LNCaP cells.@*CONCLUSION@#We can use the screening method to study membrane proteins in prostate cancer. Claudin-4 may play an important role in the pathogenesis and the development of AIPC.

Expression and clinical significance of Claudin-1 and Claudin-4 in colorectal cancer tissues / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of tight junction protein Claudin-1 and Claudin-4 in colorectal cancer tissues and its clinical significance.</p><p><b>METHODS</b>Immunohistochemical staining detected the expression of tight junction protein Claudin-1 and Claudin-4 in 60 cases of colorectal cancer and 20 normal colorectal mucosa tissue. The clinical significance was analyzed.</p><p><b>RESULTS</b>The positive rates of Claudin-1 and Claudin-4 in colorectal cancer tissues were 76.6%(46/60) and 85.0%(51/60), significantly higher than 20.0% (4/20) and 30.0%(6/20) in the normal colorectal mucosa(both P<0.01). The positive rates of Claudin-1 and Claudin-4 were associated with tumor differentiation degree, lymph node metastasis and TNM staging(all P<0.05).</p><p><b>CONCLUSIONS</b>The high expression of the Claudin-1 and Claudin-4 may play a promoting role in colorectal cancer development and progression. Claudin-1 and Claudin-4 may become prognostic markers of colorectal cancer.</p>

Target-specific cytotoxic activity of recombinant fusion toxin C-CPE-ETA' against CLDN-3,4-overexpressing ovarian cancer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to explore the possibility of creating a toxin, C-CPE-ETA', by fusing C-terminal high affinity binding domain of CPE (C-CPE) with a truncated form of Pseudomonas aeruginosa exotoxin A (ETA') and to examine whether C-CPE-ETA' could specifically target CLDN-3, 4 molecule and the targeted toxin was cytotoxic against CLDN-3,4-overexpressing ovarian cancer.</p><p><b>METHODS</b>CLDN-3 and CLDN-4 expressions were analyzed at the mRNA level in three ovarian cancer cell lines and epithelial ovarian cancer tissues from 20 patients. After transforming an expression plasmid of C-CPE-ETA' into E. coli BL21 (DE3) plysS strain, the recombinant protein was purified using His-Bind resin chromatography column and analyzed by Western blot and Coomassie blue staining. The specific binding, proapoptotic and cytolytic activities were evaluated by flow cytometry, fluorescence microscopy with the JC-1 probe and MTT assay in CLDN-3,4-overexpressing ovarian cancer cells.</p><p><b>RESULTS</b>Quantitive RT-PCR results showed there existed high levels of CLDN-3 and CLDN-4 in ovarian cancer cells, CAOV3, OVCAR3 and SKOV3. Moreover, high expressions of CLDN-3 and CLDN-4 were observed in 90.0% (18/20) and 60.0% (12/20) of ovarian cancer tissues, with an expression level 10-fold higher than that in the normal ovarian tissue. A 58 000 recombinant protein C-CPE-ETA' was demonstrated by Western blot and Coomassie blue staining. Purified and recombinant C-CPE-ETA' was bound with high affinity to CLDN-3,4-overexpressing ovarian cancer cells, CAOV3, OVCAR3 and SKOV3 cells. C-CPE-ETA' was strongly proapoptotic and cytotoxic towards the CLDN-3,4-overexpressing ovarian cancer cells. The concentration of IC(50) was 7.364 ng/ml for CAOV3 cells, 8.110 ng/ml for OVCAR3 cells and 22.340 ng/ml for SKOV3 cells, respectively. However, control CLDN-3,4-deficient cell line HUVEC was not susceptible to the recombinant C-CPE-ETA' at a concentration up to 10 µg/ml.</p><p><b>CONCLUSIONS</b>The C-CPE-ETA' protein exhibits remarkably specific cytotoxicity for CLDN-3,4-overexpressing ovarian cancer cells. Its therapeutic potential warrants further development for ovarian cancer molecular targeted therapy.</p>

TNF-alpha Downregulates E-cadherin and Sensitizes Response to gamma-irradiation in Caco-2 Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of the present study was to assess the biological effects of TNF-alpha in Caco-2 well-differentiated colon adenocarcinoma cells and to determine radiation sensitivity in order to develop TNF-alpha into a cancer therapeutic agent. MATERIALS AND METHODS: A cell viability test was conducted via a colorimetric and colony forming assay after 1 day and 3 days of incubation with TNF-alpha. Western blotting analysis and immunofluorescence staining were conducted to explore TNF-alpha-induced morphological and molecular changes in the adhesion molecules, E-cadherin and claudin-4. The effects of gamma-irradiation at a dose of 2 Gy on cell survival were evaluated by a clonogenic assay. The molecular changes in apoptosis-regulatory proteins were assessed by Western blotting. RESULTS: Caco-2 cells were highly resistant to TNF alpha-induced cell death and 2 Gy of gamma-irradiation. However, we observed the downregulation of the adherens junctional protein, E-cadherin and translocation of tight junctional protein, claudin-4 from the membrane to the cytosol induced by TNF-alpha treatment which would indicate cell-cell junction disruptions. These alterations of junctional proteins influenced the regulation of cell death in response to 2 Gy of gamma-irradiation. The combined treatment of TNF-alpha with 2 Gy of gamma-irradiation reduced the survival of Caco-2 cells by down-regulating bcl-xl and activating JNK pathways. CONCLUSION: These results suggest that TNF-alpha might be potentially applied as a therapeutic agent in order to enhance sensitivity to 2 Gy of gamma-irradiation administered in radiotherapy for the treatment of human colon cancer.

Expression of prostate stem cell antigen and Claudin-4 in human pancreatic carcinoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expressions of prostate stem cell antigen (PSCA) and Claudin-4 in human pancreatic carcinoma and to discuss its role in the ontogenesis of pancreatic cancer.</p><p><b>METHODS</b>Pancreatic carcinoma tissue microarray was constructed, containing 100 cores of 10 normal adult pancreas tissues, 12 chronic pancreatitis tissues, and 78 pancreatic carcinomas. The expressions of PSCA and Claudin-4 were detected using immunohistochemical method and the relationship between PSCA and Claudin-4 and the pancreatic carcinoma was analyzed.</p><p><b>RESULTS</b>The positive expression rates of PSCA and Claudin-4 protein in pancreatic carcinoma were 79. % and 88. % respectively. PSCA and Claudin-4 staining were more intense in malignant cells than in chronic pancreatic tissues and normal adult pancreas tissues. No evidence was found for an association between expressions of PSCA and Claudin-4 and other variables, including gender, age at surgery, and tumor grade.</p><p><b>CONCLUSIONS</b>The expressions of PSCA and Claudin-4 are related to the pancreatic carcinomas. PSCA and Claudin-4 play a role in the development of pancreatic cancer, but PSCA and Claudin-4 are not correlated with the clinical pathology of tumor.</p>

Changes of tight junction claudin-1,-3,-4 protein expression in the intestinal mucosa in patients with irritable bowel syndrome / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes of intestinal mucosal tight junction proteins claudin-1, -3, -4 in patients with irritable bowel syndrome (IBS), and elucidate its possible role in the bowel evacuation habit changes and formation in these patients.</p><p><b>METHODS</b>Western blotting was employed to determine tight junction protein claudin-1,-3,-4 levels in the intestinal mucosa of patients in the control group, diarrhea-predominant IBS (D-IBS) group and constipation-predominant IBS (C-IBS) group.</p><p><b>RESULTS</b>Compared with the control group, D-IBS patients showed significantly decreased claudin-1 protein levels in both the small intestinal and colonic mucosae (P<0.05), whereas C-IBS patients had significantly elevated claudin-1 protein levels (P<0.05). No significant difference was found in claudin-3 protein expression in the both small intestinal and colonic mucosae between the D-IBS group and the control group (P>0.05), but claudin-3 protein level was shown to increase significantly in C-IBS patients (P<0.05). Claudin-4 protein followed the same pattern of alteration as claudin-1.</p><p><b>CONCLUSION</b>Down-regulated claudin-1 and -4 expressions can be associated with bowel evacuation habit changes and formation in patients with D-IBS, but up-regulated claudin-1, -3 and -4 expressions may relate to such bowel changes in patients with C-IBS.</p>

Correlation of Decreased Expressions of Claudin 4 and E-cadherin Proteins and the Clinicopathologic Factors of Stomach Cancer

PURPOSE: We examined the expressions of claudin-4 and E-cadherin, which are known as cell adhesion-associated proteins, in stomach cancer. The relationship of their expression with the clinicopathologic factors was examined to investigate the roles of these proteins in the invasion or metastasis of stomach adenocarcinoma. METHODS: The expressions of claudin-4 and E-cadherin were examined in 73 cases of adenocarcinoma of the stomach by performing immunohistochemical staining. RESULTS: The expressions of claudin-4 and E-cadherin in the stomach adenocarcinoma were both correlated with the histologic grade, the T-stage and nodal metastasis, respectively (P<0.05). The expression of claudin-4 was significantly associated with the expression of E-cadherin. CONCLUSION: Our data suggests that claudin-4 and E-cadherin are involved in the processes of histologic differentiation, invasion and metastasis of stomach adenocarcinoma.

Expression of claudin-1, claudin-4 and zonula occludens-1 in cervical intraepithelial neoplasia and invasive squamous cell carcinoma / 대한산부인과학회지

OBJECTIVE: Cell to cell and cell to extracellular matrix interaction are crucial in tumor development and progression. Tight junction proteins such as claudins and zonula occludens-1 (ZO-1) play an important role in these processes. This study was performed to investigate the difference of expressions of claudin-1, claudin-4 and ZO-1 in low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), and invasive squamous cell carcinoma (ISCC) of the uterine cervix. METHODS: The expressions of claudin-1, claudin-4 and ZO-1 were evaluated using immunohistochemical staining in 78 cervical tissue specimens (LSIL 22 case, HSIL 36 case, and ISCC 20 case). RESULTS: Claudin-1 expression was positive in 40.9% of LSIL, in 94.0% of HSIL and in 20.0% of ISCC. The expression of claudin-1 was significantly high in HSIL (p=0.0001). Claudin-4 expression was positive in 31.8% of LSIL, in 41.7% of HSIL and in 25.0% of ISCC. The expression of claudin-4 was high in HSIL, but it was not statistically different. ZO-1 expression was positive in 13.6% of LSIL, in 41.7% of HSIL, and in 25.5% of ISCC. The expression of ZO-1 was significantly high in HSIL (p=0.011). CONCLUSION: These results indicate increased expressions of claudin-1 and ZO-1 in the HSIL that includes cervical intraepithelial neoplasia (CIN) 2 and 3, which decrease during progression to cervical cancer.

Expression of Claudin-1 and -4 in Benign Lesions and Invasive Ductal Carcinomas of the Breast

BACKGROUND: The claudins are a family of transmembrane proteins associated with tight junctions and they are critical for maintaining cell-to-cell adhesion in sheets of epithelial cells. However, their role in the progression of cancer remains largely unexplored. The aims of this study were to evaluate the expression patterns of claudin-1 and -4 in benign lesions and invasive ductal carcinomas (IDC) of the breast, and relationships between the expression of these markers and the clinicopathological characteristics in IDC patients. METHODS: We examined the claudin-1 and -4 protein expressions by performing immunohistochemical stainings in 54 benign lesions and 120 IDCs via the tissue microarray method. We evaluated the correlation between the expression of these markers and the clinicopathological characteristics of IDC. RESULTS: The expressions of claudin-1 (p=0.099) and -4 (p=0.000) were up-regulated in IDCs as compared with benign lesions. The claudin-1 expression correlated with the loss of estrogen receptor (p=0.036) and progesterone receptor (p=0.011). The claudin-4 expression correlated with lymph node metastasis (p=0.043), the nuclear grade (p=0.030), the histologic grade (p=0.007), and the loss of estrogen receptor (p=0.001) and progesterone receptor (p= 0.029). CONCLUSIONS: These results suggest that claudin-1 and -4 may play a significant role in the carcinogenesis of IDC of the breast and these may represent novel markers for this disease.