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Chinese Journal of Contemporary Pediatrics ; (12): 542-547, 2021.
Article in Chinese | WPRIM | ID: wpr-879891


Bronchopulmonary dysplasia (BPD) has the main manifestations of pulmonary edema in the early stage and characteristic alveolar obstruction and microvascular dysplasia in the late stage, which may be caused by structural and functional destruction of the lung epithelial barrier. The Claudin family is the main component of tight junction and plays an important role in regulating the permeability of paracellular ions and solutes. Claudin-18 is the only known tight junction protein solely expressed in the lung. The lack of Claudin-18 can lead to barrier dysfunction and impaired alveolar development, and the knockout of Claudin-18 can cause characteristic histopathological changes of BPD. This article elaborates on the important role of Claudin-18 in the development and progression of BPD from the aspects of lung epithelial permeability, alveolar development, and progenitor cell homeostasis, so as to provide new ideas for the pathogenesis and clinical treatment of BPD.

Humans , Infant , Infant, Newborn , Bronchopulmonary Dysplasia/etiology , Claudin-3 , Claudins/genetics , Infant, Premature , Lung , Tight Junctions
Chinese Journal of Traumatology ; (6): 374-382, 2021.
Article in English | WPRIM | ID: wpr-922704


PURPOSE@#Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro.@*METHODS@#Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD.@*RESULTS@#It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered.@*CONCLUSION@#Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.

Animals , Rats , Claudins , Nerve Regeneration , Peripheral Nerve Injuries , Schwann Cells/pathology , Sciatic Nerve , Wallerian Degeneration/pathology
Biol. Res ; 53: 12, 2020. tab, graf
Article in English | LILACS | ID: biblio-1100918


BACKGROUND: Mast cells (MCs) have been found to play a critical role during development of inflammatory bowel disease (IBD) that characterized by dysregulation of inflammation and impaired intestinal barrier function. However, the function of MCs in IBD remains to be fully elucidated. RESULTS: In our study, we used exosomes isolated from human mast cells-1 (HMCs-1) to culture with NCM460, HT-29 or CaCO2 of intestinal epithelial cells (lECs) to investigate the communication between MCs and lECs. We found that MCs-derived exosomes significantly increased intestinal epithelial permeability and destroyed intestinal barrier function, which is attributed to exosome-mediated functional miRNAs were transferred from HMCs-1 into lECs, leading to inhibit tight junction-related proteins expression, including tight junction proteins 1 (TJP1, ZO-1), Occludin (OCLN), Claudin 8 (CLDN8). Microarray and bioinformatic analysis have further revealed that a panel of miRNAs target different tight junction-related proteins. Interestingly, miR-223 is enriched in mast cell-derived exosome, which inhibit CLDN8 expression in IECs, while treatment with miR-223 inhibitor in HT-29 cells significantly reversed the inhibitory effect of HMCs-1-derived exosomes on CLDN 8 expression. Most importantly, enrichment of MCs accumulation in intestinal mucosa of patients with IBD compared with those healthy control. CONCLUSIONS: These results indicated that enrichment of exosomal miR-223 from HMCs-1 inhibited CLDN8 expression, leading to destroy intestinal barrier function. These finding provided a novel insight of MCs as a new target for therapeutic treatment of IBD.

Humans , Animals , Cattle , MicroRNAs/metabolism , Epithelial Cells/metabolism , Intestinal Mucosa/metabolism , Mast Cells/metabolism , Permeability , Inflammatory Bowel Diseases/metabolism , Cells, Cultured , Caco-2 Cells/cytology , Computational Biology , Tissue Array Analysis , Exosomes/metabolism , Claudins/metabolism , Occludin/metabolism , Zonula Occludens-1 Protein/metabolism
Chinese Journal of Biotechnology ; (12): 931-941, 2019.
Article in Chinese | WPRIM | ID: wpr-771833


Claudin proteins are the most crucial components of tight junctions, and play an essential role in maintaining cell polarity, regulating cell permeability and the intercellular ion. In recent years, many studies have shown that abnormality of claudins expression is implicated in the tumor progression. The expression correlates with tumor prognosis and can serve as a biomarker of prognosis and potential therapeutic targets. This review summarizes the current knowledge regarding claudin dysregulation in cancer and highlights the progress in claudin-based treatments.

Humans , Claudins , Therapeutic Uses , Enterotoxins , Neoplasms , Drug Therapy , Tight Junctions
Allergy, Asthma & Immunology Research ; : 25-33, 2018.
Article in English | WPRIM | ID: wpr-739390


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.

Animals , Humans , Mice , Asthma , Claudin-4 , Claudins , Cytokines , Eosinophils , Epithelial Cells , Immunoglobulin E , Inflammation , Lung , Ovum , Plasma , RNA, Small Interfering , Sodium
National Journal of Andrology ; (12): 221-225, 2018.
Article in Chinese | WPRIM | ID: wpr-689773


<p><b>Objective</b>To study the expression of CLAUDIN-11 in the testis tissue of non-obstructive azoospermia (NOA) patients with different severities and investigate its clinical significance.</p><p><b>METHODS</b>Sixty-two NOA patients were divided into a hypospermatogenesis (HS) group (n = 30) and a Sertoli cell only syndrome (SCO) group (n =32). The expression of CLAUDIN-11 in the testicular tissue of the patients was detected by immunohistochemistry, that of CLAUDIN-11 mRNA determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the levels of serum reproductive hormones measured by chemiluminescent immunoassay.</p><p><b>RESULTS</b>Immunohistochemistry showed that the expression of CLAUDIN-11 was mainly in the cytoplasm of the Sertoli cells around the seminiferous tubule wall in the HS group, but diffusely distributed in the membrane of the Sertoli cells in the SCO group. RT-qPCR revealed a significantly lower expression of CLAUDIN-11 mRNA in the HS than in the SCO group (0.008 ± 0.001 vs 0.013 ± 0.002, t = 10.616, P<0.01). The level of serum luteotropic hormone (LH) was also markedly lower in the HS than in the SCO group ([3.62 ± 1.34] vs [4.96 ± 3.10] IU/L, P<0.05) and so was that of follicle-stimulating hormone (FSH) ([5.36 ± 2.80] vs [10.65 ± 9.18] IU/L, P<0.05).</p><p><b>CONCLUSIONS</b>The up-regulated expression of CLAUDIN-11 in Sertoli cells may play an important role in the development and progression of spermatogenic dysfunction in NOA patients.</p>

Humans , Male , Azoospermia , Genetics , Metabolism , Claudins , Metabolism , Follicle Stimulating Hormone , Metabolism , Oligospermia , Genetics , Metabolism , RNA, Messenger , Metabolism , Seminiferous Tubules , Metabolism , Sertoli Cell-Only Syndrome , Genetics , Metabolism , Sertoli Cells , Metabolism , Spermatogenesis , Testis , Metabolism
São Paulo; s.n; 2016. [129] p. ilus, graf, tab.
Thesis in Portuguese | LILACS | ID: biblio-870902


Carcinomas mamários triplo-negativos correspondem ao grupo heterogêneo de neoplasias mamárias caracterizadas pela ausência de expressão dos receptores de estrogênio e progesterona e sem amplificação ou superexpressão do HER2. São mais prevalentes em mulheres jovens e em afrodescendentes. Eles se associam frequentemente ao fenótipo basal-símile determinado geneticamente, entretanto, incluem também outros tipos moleculares intrínsecos. Metodologias de análise genética de novas gerações têm permitido sua estratificação em subgrupos distintos, o que justifica a heterogeneidade clínica deste grupo de neoplasias. A identificação desses subgrupos através de marcadores imunoistoquímicos de aplicação prática ainda é pouco explorada, embora seja uma ferramenta promissora na sua estratificação e determinação de alvos terapêuticos. OBJETIVOS: Nosso objetivo é explorar os perfis imunoistoquímicos dos carcinomas mamários triplo-negativos em mulheres com idade até 45 anos e investigar possíveis diferenças entre as cinco regiões geográficas brasileiras. MÉTODOS: Selecionamos 118 amostras de tumores de pacientes com idade até 45 anos, com carcinoma invasivo, blocos de parafina disponíveis e perfil imunoistoquímico triplo-negativo, procedentes das cinco regiões geográficas. Estes casos foram revisados quanto à determinação de tipo e grau histológico e as seguintes características anatomopatológicas: contorno do tumor, presença e fração do componente "in situ", embolização vascular peritumoral, tipo e grau da reação estromal, presença de necrose tumoral e formação de túbulos pela neoplasia. Foram selecionadas áreas representativas do tumor para construção de blocos de microarranjos de tecido para estudo imunoistoquímico. Foram pesquisados os seguintes marcadores: citoqueratinas basais 5/6 e 14, citoqueratinas luminais 8 e 18, receptor do fator de crescimento epidérmico (EGFR ou HER1), receptor de androgênio, e-caderina, catenina-beta,...

Triple-negative breast carcinomas (TNBC) correspond to a heterogeneous group of neoplasia characterized by the lack of expression of estrogen and progesterone receptors, and by the absence of amplification or overexpression of HER2. They are more prevalent among African descendants and younger women. They are often associated with the basal-like genetic phenotype; however, other intrinsic molecular types are included. Genomic analyses of next-generation methods have allowed stratification of TN breast carcinomas into distinct subgroups, explaining the clinical heterogeneity of this group of neoplasias. The identification of these subgroups by immunohistochemical markers is not well explored, although it represents a potential useful tool for the stratification and determination of therapeutic targets. OBJECTIVES: Our aim is to explore the TNBC immunohistochemical profile in patients of 45 year-old or younger, and to investigate possible differences among the five Brazilian geographic regions. METHODS: We've selected 118 samples of tumors from patients up to 45 years-old from five Brazilian geographic regions, with invasive carcinoma, available paraffin blocks, and triple-negative immunohistochemical profile. All the cases were reviewed as for determination of histologic type and grading, and the following pathological features: tumor contour, presence and percentage of in situ component, peritumoral vascular embolization, type and grade of stromal reaction, presence of tumoral necrosis, and tubule formation by neoplasia. Representative tumor areas were selected for tissue microarray construction for immunohistochemical study. The following markers were studied: Basal cytokeratins 5/6 and 14; luminal cytokeratins 8 and 18; Epidermal growth factor receptor (EGFR or HER1); androgen receptor; e-cadherin; catenin-beta; claudins (3,4 and 7); vimentin; smooth-muscle actin; p63, ALDH1, and Ki-67. According to the expression of the markers, the tumors...

Humans , Female , Adult , Breast Neoplasms , Claudins , Epidemiology , Immunohistochemistry , Keratins , Lymphocytes, Tumor-Infiltrating , Triple Negative Breast Neoplasms
Actual. osteol ; 12(2): 97-106, 2016. graf, tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1372249


Previamente hemos demostrado que la diabetes mellitus tipo 1 experimental (D.m.1) inducida por estreptozotocina (STZ) produce estrés oxidativo intestinal en las primeras etapas de la enfermedad, lo que conduce a la inhibición de la absorción intestinal de Ca+2, alterando la vía transcelular del transporte del catión. El objetivo de este trabajo fue estudiar la vía paracelular del transporte del Ca+2 y analizar si la D.m.1 induce estrés nitrosativo a nivel duodenal. Se utilizaron ratas Wistar machos a las que se inyectaron 60 mg STZ/kg de peso corporal; se sacrificaron a los 30 días postratamiento. Se determinó la expresión génica y proteica de claudina 2 y 12, proteínas involucradas en el transporte paracelular del Ca+2. En la mucosa duodenal se determinó el contenido de óxido nítrico (NO) y la expresión proteica de óxido nítrico sintasa inducible (iNOS). Los resultados revelaron que la expresión génica de claudina 2 en las ratas diabéticas fue más del doble en comparación con la de los controles, mientras que la expresión génica de claudina 12 fue similar en ambos grupos. La expresión proteica de claudina 2 y 12 aumentó en las ratas diabéticas. El contenido de NO fue similar en ambos grupos; sin embargo, la expresión proteica de iNOS fue mayor en las ratas diabéticas en comparación con la de las ratas controles. En conclusión, la D.m.1 experimental se acompaña de estrés oxidativo y de aumento en la expresión proteica de iNOS, alterándose la vía paracelular de absorción de Ca+2 como un mecanismo compensatorio. (AU)

We have previously shown that experimental type 1 diabetes mellitus (D.m.1) produced by streptozotocin (STZ) in rats causes intestinal oxidative stress in the early stages of the disease, which leads to the inhibition of intestinal Ca2+ absorption, altering the transcellular Ca2+ pathway. The aim of this work was to study the paracellular Ca2+ pathway and analyze if D.m.1 induces duodenal nitrosative stress. The animals were assigned to two groups: 1) control rats, and 2) STZ-induced diabetic rats (60 mg/kg b.w.). Rats were sacrificed 30 days after induction of diabetes. The gene and protein expression of claudin 2 and 12, proteins involved in paracellular Ca2+ pathway, was determined as well as the nitric oxide (NO) content and protein expression of iNOS in rat duodenum mucosa. The results revealed that claudin 2 expression was more that double in diabetic rats compared to control rats at 30 days, while the gene expression of claudin 12 was similar in both groups. The protein expression of claudin 2 and 12 increased in the diabetic rats. NO content was similar in both groups, but the iNOS protein expression was enhanced in diabetic rats. To conclude, the experimental type I D.m.1 is accompanied by duodenal oxidative stress, increase iNOS protein expression and alteration of the paracellular Ca2+ pathway as a compensatory mechanism. (AU)

Animals , Male , Rats , Calcium Metabolism Disorders/etiology , Diabetes Mellitus, Experimental/enzymology , Nitric Oxide Synthase Type II/metabolism , Intestinal Absorption , Phosphates/blood , Blood Glucose , Gene Expression , Calcium/blood , Rats, Wistar , Oxidative Stress , Diabetes Mellitus, Experimental/complications , Disease Models, Animal , Claudins/genetics
Chinese Medical Journal ; (24): 442-447, 2016.
Article in English | WPRIM | ID: wpr-328225


<p><b>BACKGROUND</b>Claudin-5, claudin-9, and claudin-11 are expressed in endothelial cells to constitute tight junctions, and their deficiency may lead to hyperpermeability, which is the initiating process and pathological basis of cardiovascular disease. Although tongxinluo (TXL) has satisfactory antianginal effects, whether and how it modulates claudin-5, claudin-9, and claudin-11 in hypoxia-stimulated human cardiac microvascular endothelial cells (HCMECs) have not been reported.</p><p><b>METHODS</b>In this study, HCMECs were stimulated with CoCl2to mimic hypoxia and treated with TXL. First, the messenger RNA (mRNA) expression of claudin-5, claudin-9, and claudin-11 was confirmed. Then, the protein content and distribution of claudin-9, as well as cell morphological changes were evaluated after TXL treatment. Furthermore, the distribution and content histone H3K9 acetylation (H3K9ac) in the claudin-9 gene promoter, which guarantees transcriptional activation, were examined to explore the underlying mechanism, by which TXL up-regulates claudin-9 in hypoxia-stimulated HCMECs.</p><p><b>RESULTS</b>We found that hypoxia-suppressed claudin-9 gene expression in HCMECs (F = 7.244; P = 0.011) and the hypoxia-suppressed claudin-9 could be reversed by TXL (F = 61.911; P = 0.000), which was verified by its protein content changes (F = 29.142; P = 0.000). Moreover, high-dose TXL promoted the cytomembrane localization of claudin-9 in hypoxia-stimulated HCMECs, with attenuation of cell injury. Furthermore, high-dose TXL elevated the hypoxia-inhibited H3K9ac in the claudin-9 gene promoter (F = 37.766; P = 0.000), activating claudin-9 transcription.</p><p><b>CONCLUSIONS</b>The results manifested that TXL reversed the hypoxia-suppressed claudin-9 by elevating H3K9ac in its gene promoter, playing protective roles in HCMECs.</p>

Humans , Cell Hypoxia , Cells, Cultured , Claudins , Genetics , Drugs, Chinese Herbal , Pharmacology , Endothelial Cells , Metabolism , Histones , Metabolism , Myocardium , Cell Biology , Metabolism , Promoter Regions, Genetic
Journal of Veterinary Science ; : 445-451, 2016.
Article in English | WPRIM | ID: wpr-110500


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.

Animals , Female , Architectural Accessibility , Blotting, Western , Claudin-1 , Claudin-2 , Claudin-4 , Claudin-5 , Claudins , Colic , Duodenum , Horse Diseases , Horses , Immunohistochemistry , Kidney , Liver , Lung , Methods , Organ Specificity , Ovary , Tight Junctions , Transportation , Uterus
Rev. chil. pediatr ; 86(4): 264-269, ago. 2015. graf, tab
Article in Spanish | LILACS | ID: lil-764083


Introducción: La alopecia infantil es una afección poco frecuente en la consulta dermatológica pediátrica. Su etiología es variable según el grupo etario estudiado. El objetivo fue estudiar la causa de alopecia en niños en 2 hospitales pediátricos de referencia nacional en Chile. Pacientes y método: Análisis descriptivo de registros clínicos del total de pacientes atendidos entre enero de 2007 y junio de 2010 en los Servicios de Dermatología de los Hospitales Roberto del Río y Luis Calvo Mackenna. Se incluyeron pacientes con diagnóstico clínico de alopecia. Resultados: Se encontraron 345 registros clínicos, 179 varones (51,9%). La mediana de edad fue 72 meses. Los diagnósticos más prevalentes fueron alopecia areata (AA) (36,8%), tiña capitis (TC) (21%), nevo sebáceo (13,2%) y efluvio telógeno (8,7%). Según el grupo etario predominaron en recién nacidos: aplasia cutis y nevo sebáceo; en lactantes, preescolares y escolares: nevo sebáceo, AA y TC. En escolares se agregó tricotilomanía. En adolescentes nevo sebáceo, AA y efluvio telógeno. Se observó una correlación significativa entre AA con enfermedad autoinmune, enfermedad tiroidea, alteraciones ungueales, enfermedad psiquiátrica y síndrome de Down. En TC el agente etiológico más prevalente fue Microsporum Canis (86,6%). La tricotilomanía se correlacionó con enfermedad psiquiátrica significativamente. Conclusiones: Las principales causas de alopecia infantil fueron adquiridas y no cicatriciales. La etiología varía de acuerdo al grupo etario estudiado. Algunos tipos de alopecia infantil presentaron alta prevalencia de enfermedad psiquiátrica.

Introduction: Childhood alopecia is a relative rare event in general paediatric dermatology practice. Hair loss in children may have multiple causes, and there are different types of alopecia according to age groups. The aim of the study was to describe the clinical and epidemiological profile of alopecia in children from two Chilean paediatric hospitals. Patients and method: Descriptive analysis of clinical records of patients from the Dermatology Department of Roberto del Rio and Luis Calvo Mackenna Hospitals between January 2007 and June 2010. Patients with clinical diagnosis of alopecia were included. Results: A total of 345 clinical records were analysed, with 179 males (51.9%). The median age was 72 months. Overall, the most common diagnoses were: alopecia areata (AA), (36.8%), tinea capitis (TC), (21%), nevus sebaceous (13.2%), and tellogen effluvium (8.7%). According to age groups, in newborns, the most common causes were aplasia cutis and nevus sebaceous. In toddlers, pre-school and school children, the principal causes were nevus sebaceous, AA and TC. Trichotillomania was also significant in school children. In adolescents, nevus sebaceous, AA and tellogen effluvium were the most frequent diagnoses. AA was statistically associated with autoimmune disease, thyroid disease, nail disorder, psychiatric disease, and Down's syndrome. The most common aetiological agent in TC was M. canis (86.6%). Trichotillomania was also statistically associated to psychiatric disorders. Conclusions: In this study, the main causes of alopecia in children were acquired and non-scarring alopecia. In our results, the type of alopecia varies according to age group. Some types of childhood alopecia showed a close correlation to psychiatric disorders.

Humans , Cell Membrane Permeability/physiology , Claudins/metabolism , Epithelial Cells/metabolism , Epithelial Cells/physiology , Harringtonines/metabolism , Intestines/metabolism , Protein Isoforms/metabolism , Cell Line, Tumor , Dextrans/metabolism , /analogs & derivatives , /metabolism , Intestines/physiology , Tight Junctions/metabolism , Tight Junctions/physiology , Transcription, Genetic/physiology
Rev. Assoc. Med. Bras. (1992) ; 61(1): 81-85, Jan-Feb/2015.
Article in English | LILACS | ID: lil-744723


The role of adhesion molecules is very important both in the activation of carcinogenesis and in the differentiation of subtypes of breast carcinoma, aiding in diagnosis, prognosis and therapeutic choice in these tumors. Therefore, understanding the functions and interrelationships among these molecules is crucial to the pathologist, who often uses these factors as a resource to differentiate tumors and further classify them according to a molecular point of view. Our goal is to describe the applicability and the difficulties encountered by the pathologist in the diagnosis of breast carcinoma, discussing the most commonly used markers of adhesion in routine analyses.

O papel das moléculas de adesão é de suma importância tanto na ativação da carcinogênese quanto na diferenciação dos subtipos de carcinomas mamários, auxiliando no diagnóstico, no prognóstico e na escolha terapêutica nessas neoplasias. Portanto, a compreensão das funções e das inter-relações entre essas moléculas é de suma importância para o patologista, que, muitas vezes, as utiliza como recurso na diferenciação dos tumores e, consequentemente, elas auxiliam em uma posterior classificação do ponto de vista molecular. O objetivo é descrever a aplicabilidade e as dificuldades encontradas pelo médico patologista no diagnóstico de carcinoma mamário, discutindo os marcadores de adesividade mais utilizados na rotina.

Female , Humans , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Adhesion Molecules/metabolism , Biomarkers, Tumor/metabolism , Cell Transformation, Neoplastic , Cadherins/metabolism , Claudins/metabolism , Immunohistochemistry , Metalloproteases/metabolism , Mucins/metabolism
National Journal of Andrology ; (12): 1110-1115, 2015.
Article in Chinese | WPRIM | ID: wpr-304765


<p><b>OBJECTIVE</b>To investigate the effects of the combination of musk and olibanum on the tight junction protein expressions in prostatic epithelial cells of normal and chronic prostatitis (CP) rats.</p><p><b>METHODS</b>Eighty male SD rats were randomly divided into 8 groups of equal number: normal control, normal musk, normal olibanum, normal musk + olibanum, CP model control, CP model musk, CP model olibanum, and CP model musk + olibanum. At 60 days after modeling, the rats in the control, musk, olibanum, and musk + olibanum groups were treated intragastrically with normal saline, musk (0.021 g per kg body weight per day), olibanum (1.05 g per kg body weight per day), or musk + olibanum respectively, all for 3 days. Then, all the rats were sacrificed and their prostate tissues harvested for detection of the expressions of the tight junction proteins Claudin-1, Claudin-3, Occludin, and ZO-1 in the prostatic epithelial cells by immunohistochemical staining.</p><p><b>RESULTS</b>In the CP models, only the expression of Claudin-1 was significantly increased. In the normal rats, the expression of Claudin-1 was remarkably upregulated after treated with musk (824.6 ± 393.3, P < 0.05), olibanum (982.0 ± 334.0, P < 0.05), and musk + olibanum (1088.1 ± 640.2, P < 0.01); that of Claudin-3 was elevated markedly by olibanum (1 009.5 ± 243.6, P < 0.05) and insignificantly by musk (597.5 ± 80.7), but the increasing effect of olibanum was reduced by musk + olibanum (678.4 ± 255.1). No statistically significant differences were found in the expression of Occludin among the rats treated with musk (693.0 ± 424.8), olibanum (732.1 ± 302.0), and musk + olibanum (560.2 ± 202.3), or in that of ZO-1 in the animals treated with musk (290.0 ± 166.8) and olibanum (419.7 ± 108.1), but the latter was markedly decreased in the musk + olibanum group (197.7 ± 98.2, P < 0.05). In the CP rat models, both the expressions of Claudin-1 (823.0 ± 100.1, P < 0.01) and Occludin (1160.0 ± 32.2, P < 0.05) were significantly increased. The expression of Claudin-1 was remarkably down-regulated by musk (764.9 ± 179.0), olibanum (468.4 ± 220.4), and musk + olibanum (335.1 ± 204.0) (all P < 0.05), but that of Claudin-3 up-regulated by musk (744.6 ± 94.5) and olibanum (700.1 ± 223.7) (both P < 0.05). The expression of Occludin was reduced by musk (615.0 ± 221.0), olibanum (749.6 ± 321.7), and musk + olibanum (505.8 ± 523.7), while that of ZO-1 increased by olibaum (443.2 ± 44.9) and decreased by musk + olibanum (213.5 ± 24.9, P < 0.05).</p><p><b>CONCLUSION</b>In physiological and pathological conditions, the combination of musk and olibanum acts on the expressions of tight junction proteins in prostate epithelial cells in a selective and dual-targeting manner, promoting their permeability by down-regulating the expression of ZO-1 and maintaining their structural stability by regulating the expressions of Claudin-1, Claudin-3, and Occludin.</p>

Animals , Male , Rats , Claudins , Metabolism , Down-Regulation , Epithelial Cells , Fatty Acids, Monounsaturated , Chemistry , Frankincense , Chemistry , Occludin , Metabolism , Prostate , Cell Biology , Prostatitis , Rats, Sprague-Dawley , Tight Junction Proteins , Metabolism , Up-Regulation
Intestinal Research ; : 227-232, 2015.
Article in English | WPRIM | ID: wpr-96061


Proton pump inhibitors (PPIs) are widely used though an association with hypomagnesaemia and hypocalcaemia has only been described since 2006. Patients typically present after years of stable dosing with musculoskeletal, neurological or cardiac arrhythmic symptoms, but it is likely that many cases are under-recognised. Magnesium levels resolve rapidly on discontinuation of PPI therapy and hypomagnesaemia recurs rapidly on rechallenge with any agent in the class. The cellular mechanisms of magnesium homeostasis are increasingly being understood, including both passive paracellular absorption through claudins and active transcellular transporters, including the transient receptor potential channels (TRPM6) identified in the intestine and nephron. PPIs may alter luminal pH by modulating pancreatic secretions, affecting non-gastric H+K+ATPase secretion, altering transporter transcription or channel function. A small reduction in intestinal absorption appears pivotal in causing cumulative deficiency. Risk factors have been associated to help identify patients at risk of this effect but clinical vigilance remains necessary for diagnosis.

Humans , Absorption , Claudins , Diagnosis , Fatigue , Homeostasis , Hydrogen-Ion Concentration , Intestinal Absorption , Intestines , Magnesium , Nephrons , Phenobarbital , Proton Pump Inhibitors , Risk Factors , Transcytosis , Transient Receptor Potential Channels
Gut and Liver ; : 734-740, 2015.
Article in English | WPRIM | ID: wpr-67332


BACKGROUND/AIMS: This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. METHODS: Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. RESULTS: The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%+/-1.2% in controls and was significantly increased to 7.2%+/-1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. CONCLUSIONS: There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.

Animals , Rats , Apoptosis/physiology , Claudins/metabolism , Colitis/chemically induced , Colon/immunology , Dextran Sulfate , Intestinal Mucosa/physiopathology , Lactulose/metabolism , Mannitol/metabolism , Mannose-Binding Lectin/immunology , Permeability , Rats, Sprague-Dawley , Sucrose/analogs & derivatives , Up-Regulation
Journal of Biomedical Research ; : 98-103, 2015.
Article in English | WPRIM | ID: wpr-155588


Tight junctions (TJs) form continuous intercellular contacts in intercellular junctions. TJs involve integral proteins such as occludin (OCLN) and claudins (CLDNs) as well as peripheral proteins such as zona occludens-1 (ZO-1) and junctional adhesion molecules (JAMs). TJs control paracellular transportation across cell-to-cell junctions. Although TJs have been studied for several decades, comparison of the transcriptional-translational levels of these molecules in canine organs has not yet been performed. In this study, we examined uterine expression of CLDNs, OCLN, junction adhesion molecule-A, and ZO-1 in canine. Expression levels of canine uterine TJ proteins, including CLDN1, 2, 4, 5, JAM-A, ZO-1, and OCLN, were measured using reverse transcription PCR, real-time PCR, and Western blotting, whereas TJs distribution was determined by immunohistochemistry. The mRNA and protein expression levels of OCLN, CLDN-1, 4, JAM-1, and ZO-1 were identified in the uterus. Immunohistochemistry demonstrated that TJs were localized to the endometrium and/or myometrium of the uterus. Our results show that canine TJ proteins, including CLDNs, OCLN, JAM-A, and ZO-1, were expressed in the canine uterus. Taken together, these proteins may perform unique physiological roles in the uterus. Therefore, these findings may serve as a basis for further studies on TJ proteins and their roles in the physiological or pathological condition of the canine uterus.

Animals , Dogs , Female , Mice , Blotting, Western , Claudins , Endometrium , Herpes Zoster , Immunohistochemistry , Intercellular Junctions , Junctional Adhesion Molecules , Myometrium , Occludin , Physiology , Polymerase Chain Reaction , Real-Time Polymerase Chain Reaction , Reverse Transcription , RNA, Messenger , Tight Junctions , Transportation , Uterus
J. bras. nefrol ; 36(3): 401-405, Jul-Sep/2014. tab, graf
Article in English | LILACS | ID: lil-725509


Introduction: Familial Hypomagnesaemia with hypercalciuria and nephrocalcinosis, with severe ocular impairment secondary to claudin-19 mutation, is a rare recessive autossomic disorder. Its spectrum includes renal Mg2+ wasting, medullary nephrocalcinosis and progressive chronic renal failure in young people. Objective: To report a case of kidney transplantation father to daughter in a familial occurrence of severe bilateral nephrocalcinosis associated with ocular impairment in a non-consanguineous Brazilian family, in which two daughters had nephrocalcinosis and severe retinopathy. Methods: The index case, a 19 years-old female, had long-lasting past medical history of recurrent urinary tract infections, and the abdominal X-ray revealed bilateral multiple renal calcifications as well as ureteral lithiasis, and she was under haemodialysis. She had the diagnosis of retinitis pigmentosa in the early neonatal period. The other daughter (13 years-old) had also nephrocalcinosis with preserved kidney function, retinopathy with severe visual impairment, and in addition, she exhibited hypomagnesaemia = 0.5 mg/dL and hypercalciuria. The other family members (mother, father and son) had no clinical disease manifestation. Mutation analysis at claudin-19 revealed two heterozygous missense mutations (P28L and G20D) in both affected daughters. The other family members exhibited mutant monoallelic status. In despite of that, the index case underwent intrafamilial living donor kidney transplantation (father). Conclusion: In conclusion, the disease was characterized by an autosomal recessive compound heterozygous status and, after five years of donation the renal graft function remained stable without recurrence of metabolic disturbances or nephrocalcinosis. Besides, donor single kidney Mg2+ and Ca2+ homeostasis associated to monoallelic status did not affect the safety and the usual living donor post-transplant clinical course. .

Introdução: Hipomagnesemia familiar com hipercalciúria e nefrocalcinose, com grave envolvimento ocular, por mutação no gene da claudina-19, é uma doença rara autossômica recessiva. Seu espectro inclui perda renal de magnésio, nefrocalcinose medular e doença renal progressiva em crianças e adolescentes. Objetivo: Relatar um caso de transplante renal pai para filha em uma ocorrência familiar de nefrocalcinose bilateral grave associada com comprometimento ocular em uma família brasileira não consangüínea, na qual duas filhas apresentavam nefrocalcinose e retinopatia severa. Métodos: O caso índice, uma mulher de 19 anos de idade, tinha longa história pregressa de infecção urinária de repetição, o raio-X abdominal revelava calcificações renais múltiplas bilaterais, bem como litíase ureteral, e estava sob hemodiálise. Havia um diagnóstico prévio de retinite pigmentosa no período neonatal precoce. A outra filha (13 anos de idade) também apresentava nefrocalcinose com função renal preservada, retinopatia com grave deficiência visual, e além disso, ela exibia hipomagnesemia = 0,5 mg/dL e hipercalciúria. Os outros membros da família (mãe, pai e filho) não tinham nenhuma manifestação clínica da doença. A análise mutacional no gene da claudin-19 revelou duas mutações heterozigotas (P28L e G20D) em ambas as filhas afetadas. Os outros membros da família apresentavam estado mutante monoalélico. Apesar disso, o caso índice foi submetido a transplante de rim com doador vivo intrafamiliar (pai). Conclusão: Em conclusão, a doença foi caracterizada por um estado heterozigoto recessivo composto autossômico e após cinco anos de doação a função do enxerto ...

Female , Humans , Young Adult , Claudins/genetics , Eye Diseases, Hereditary/genetics , Eye Diseases, Hereditary/surgery , Kidney Transplantation , Mutation , Renal Tubular Transport, Inborn Errors/genetics , Renal Tubular Transport, Inborn Errors/surgery , Family , Time Factors , Tissue Donors
Indian J Hum Genet ; 2013 July-Sept ;19 (3): 331-336
Article in English | IMSEAR | ID: sea-156586


BACKGROUND: Hearing loss is the most prevalent human genetic sensorineural defect. Mutations in the CLDN14 gene, encoding the tight junction claudin 14 protein expressed in the inner ear, have been shown to cause non‑syndromic recessive hearing loss DFNB29. AIM: We describe a Moroccan SF7 family with non‑syndromic hearing loss. We performed linkage analysis in this family and sequencing to identify the mutation causing deafness. MATERIALS AND METHODS: Genetic linkage analysis, suggested the involvement of CLDN14 and KCNE1 gene in deafness in this family. Mutation screening was performed using direct sequencing of the CLDN14 and KCNE1 coding exon gene. RESULTS: Our results show the presence of c.11C>T mutation in the CLDN14 gene. Transmission analysis of this mutation in the family showed that the three affected individuals are homozygous, whereas parents and three healthy individuals are heterozygous. This mutation induces a substitution of threonine to methionine at position 4. CONCLUSION: These data show that CLDN14 gene can be i mplicated in the development of hearing loss in SF7 family; however, the pathogenicity of c.11C>T mutation remains to be determined.

Amino Acid Substitution , Base Sequence , Claudins/genetics , DNA Mutational Analysis , Family/genetics , Gene Frequency , Hearing Loss, Sensorineural/genetics , Hearing Loss, Sensorineural/pathology , Heterozygote , Homozygote , Humans , Morocco , Mutation, Missense , Sequence Analysis, DNA/methods
São Paulo med. j ; 131(2): 71-79, abr. 2013. tab, graf
Article in English | LILACS | ID: lil-671680


CONTEXT AND OBJECTIVE The possible role of adhesion molecules in early breast carcinogenesis has been shown in the literature. We aimed to analyze early adhesion imbalances in non-nodular breast lesions and their association with precursor lesions, in order to ascertain whether these alterations exist and contribute towards early carcinogenesis. DESIGN AND SETTING Retrospective cross-sectional study based on medical records at a private radiological clinic in São Paulo, Brazil. METHODS We retrospectively reviewed the medical records of all consecutive women attended between August 2006 and July 2007 who presented mammographic evidence of breast microcalcifications classified as Breast Imaging Reporting and Data System Atlas (BI-RADS) type 4. These women underwent stereotaxic biopsy. Clinical, radiological and pathological data were collected, and immunohistochemical assays searched for claudin, paxillin, FRA-1 and HER-2. RESULTS Over this period, 127 patients were evaluated. Previous BI-RADS diagnoses showed that 69 cases were in category 4A, 47 in 4B and 11 in 4C. Morphological assessment showed benign entities in 86.5%. Most of the benign lesions showed preserved claudin expression, associated with paxillin (P < 0.001). Paxillin and HER-2 expressions were correlated. FRA-1 expression was also strongly associated with HER-2 expression (P < 0.001). CONCLUSIONS Although already present in smaller amounts, imbalance of adhesion molecules is not necessarily prevalent in non-nodular breast lesions. Since FRA-1 expression reached statistically significant correlations with radiological and morphological diagnoses and HER-2 status, it may have a predictive role in this setting. .

CONTEXTO E OBJETIVO A literatura tem mostrado a importância de moléculas de adesão na carcinogênese precoce de mama. Objetivamos analisar desequilíbrios precoces de adesão em lesões não nodulares da mama e associação com lesões precursoras, a fim de verificar se essas alterações existem e contribuem com a carcinogênese. TIPO DE ESTUDO E LOCAL Estudo retrospectivo baseado em prontuários médicos, numa clínica radiológica privada em São Paulo, Brasil. MÉTODOS Revisamos retrospectivamente prontuários de todas as mulheres consecutivamente atendidas com evidência mamográfica de microcalcificações mamárias, classificadas como tipo 4 do Breast Imaging Reporting and Data System Atlas (BI-RADS) entre agosto de 2006 e julho de 2007. Elas foram submetidas a biópsia estereotáxica. Dados clínicos, radiológicos e histopatológicos foram coletados e ensaios de imunoistoquímica procuraram por claudina, paxilina, HER-2 e FRA-1. RESULTADOS No período, 127 pacientes foram avaliadas. Diagnósticos de BI-RADS anteriores tinham 69 casos na categoria 4A, 47 em 4B, e 11 em 4C. A avaliação morfológica mostrou entidades benignas em 86,5%. A maioria das lesões benignas mostrou expressão preservada de claudina, associada a paxilina (P < 0,001). Expressões de paxilina e HER-2 foram correlacionadas. Expressão de FRA-1 associou-se à de HER-2 (P < 0,001). CONCLUSÕES Embora já presente em menor quantidade, o desequilíbrio de moléculas de adesão não é necessariamente prevalente em lesões mamárias nodulares e talvez a expressão de FRA-1 possa ter um papel preditivo neste cenário, uma vez que atingiu correlações ...

Female , Humans , Calcinosis/metabolism , Claudins/analysis , Paxillin/analysis , Proto-Oncogene Proteins c-fos/analysis , /analysis , Antibodies, Monoclonal , Breast Neoplasms/chemistry , Breast Neoplasms/pathology , Breast/pathology , Calcinosis/pathology , Epidemiologic Methods , Hyperplasia/metabolism , Hyperplasia/pathology , Precancerous Conditions/chemistry , Precancerous Conditions/pathology , Biomarkers, Tumor/analysis