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1.
Acta Physiologica Sinica ; (6): 931-939, 2021.
Article in Chinese | WPRIM | ID: wpr-921298

ABSTRACT

Endothelial tight junctions (TJs) serve as an important barrier in vascular endothelial structure and maintain vascular function homeostasis. Occludin, the most representative tight junction protein, is involved in sealing cell connections and maintaining the integrity and permeability of vascular endothelium. Recent studies have shown that alterations in the expression, distribution, and structure of endothelial TJs may lead to many related vascular diseases and pathologies (such as stroke, atherosclerosis, and pulmonary hypertension etc.). Here, we reviewed the research advances on the relationship between occludin and vascular endothelial injury, including the biological information of occludin, the signal pathways that occludin exerts the protective effect of vascular endothelium, and the relationship between occludin and vascular endothelial injury-related diseases.


Subject(s)
Endothelium, Vascular , Occludin/genetics , Signal Transduction , Tight Junctions
2.
Article in Chinese | WPRIM | ID: wpr-887504

ABSTRACT

OBJECTIVE@#To observe the effect of acupoint thread-embedding on tight junction of intestinal mucosal epithelial barrier in rats with ulcerative colitis (UC) under the state of "deficiency and stasis", and to explore its mechanism.@*METHODS@#Sixty male SD rats were randomly divided into a control group (@*RESULTS@#Compared with the control group, in the model group the body weight was decreased (@*CONCLUSION@#The thread-embedding could repair the tight junction of intestinal mucosa epithelium and reduce the permeability of intestinal mucosa epithelium, which may be related to the decrease of the expression of CaMKⅡ, MLCK and other protein kinases.


Subject(s)
Acupuncture Points , Animals , Colitis, Ulcerative/therapy , Epithelium , Intestinal Mucosa , Male , Rats , Rats, Sprague-Dawley , Tight Junctions
3.
Article in English | WPRIM | ID: wpr-878442

ABSTRACT

OBJECTIVES@#This study aims to investigate the effects of ionizing radiation on the secretion of the paracellular pathway in rat submandibular glands (SMGs) and reveal the changes in the tight junction (TJ) protein claudin-4.@*METHODS@#A total of 24 Wistar rats were randomly divided into control and irradiation groups. The irradiation groups were further divided into 1, 4, and 12 weeks groups after irradiation. One-time 20 Gy irradiation was given to the SMG area on the experimental side of the irradiation group. At 1, 4, and 12 weeks after irradiation, the secretion of SMGs was measured using the Schirmer's test. The pathological changes in the gland tissues were observed under light microscopy after hematoxylin⁃eosin (HE) staining. The changes in the TJ ultrastructure were observed under transmission electron microscopy. The immunofluorescence staining and Western blot were used to detect the expression levels of muscarinic acetylcholine M3 receptor, aquaporin 5 (AQP5), and claudin-4 protein.@*RESULTS@#At 1, 4, and 12 weeks after irradiation, the secretion of SMGs in the irradiation group was significantly decreased and lower than that in the control group (@*CONCLUSIONS@#The changes in the TJ structure, the upregulation of the claudin-4 expression, and the damage in the paracellular pathway were involved in the hyposecretion of SMGs after irradiation.


Subject(s)
Animals , Microscopy, Electron, Transmission , Radiation, Ionizing , Rats , Rats, Wistar , Submandibular Gland , Tight Junctions
4.
Article in Chinese | WPRIM | ID: wpr-879891

ABSTRACT

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.


Subject(s)
Bronchopulmonary Dysplasia/etiology , Claudin-3 , Claudins/genetics , Humans , Infant , Infant, Newborn , Infant, Premature , Lung , Tight Junctions
5.
Article in English | WPRIM | ID: wpr-762183

ABSTRACT

PURPOSE: The effect of air pollution-related particulate matter (PM) on epithelial barrier function and tight junction (TJ) expression in human nasal mucosa has not been studied to date. This study therefore aimed to assess the direct impact of PM with an aerodynamic diameter less than 2.5 μm (PM2.5) on the barrier function and TJ molecular expression of human nasal epithelial cells. METHODS: Air-liquid interface cultures were established with epithelial cells derived from noninflammatory nasal mucosal tissue collected from patients undergoing paranasal sinus surgery. Confluent cultures were exposed to 50 or 100 µg/mL PM2.5 for up to 72 hours, and assessed for 1) epithelial barrier integrity as measured by transepithelial resistance (TER) and permeability of fluorescein isothiocyanate (FITC) 4 kDa; 2) expression of TJs using real-time quantitative polymerase chain reaction and immunofluorescence staining, and 3) proinflammatory cytokines by luminometric bead array or enzyme-linked immunosorbent assay. RESULTS: Compared to control medium, 50 and/or 100 µg/mL PM2.5-treatment 1) significantly decreased TER and increased FITC permeability, which could not be restored by budesonide pretreatment; 2) significantly decreased the expression of claudin-1 messenger RNA, claudin-1, occludin and ZO-1 protein; and 3) significantly increased production of the cytokines interleukin-8, TIMP metallopeptidase inhibitor 1 and thymic stromal lymphopoietin. CONCLUSIONS: Exposure to PM2.5 may lead to loss of barrier function in human nasal epithelium through decreased expression of TJ proteins and increased release of proinflammatory cytokines. These results suggest an important mechanism of susceptibility to rhinitis and rhinosinusitis in highly PM2.5-polluted areas.


Subject(s)
Asthma , Budesonide , Claudin-1 , Cytokines , Enzyme-Linked Immunosorbent Assay , Epithelial Cells , Fluorescein , Fluorescein-5-isothiocyanate , Fluorescent Antibody Technique , Humans , Interleukin-8 , Mucous Membrane , Nasal Mucosa , Occludin , Particulate Matter , Permeability , Polymerase Chain Reaction , Rhinitis , RNA, Messenger , Tight Junctions
6.
Annals of Dermatology ; : 130-140, 2020.
Article in English | WPRIM | ID: wpr-811085

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is recognized as a common inflammatory skin disease and frequently occurred in Asian and Black individuals.OBJECTIVE: Since the limitation of dataset associated with human severe AD, this study aimed to screen potential novel biomarkers involved in mild AD.METHODS: Expression profile data (GSE75890) were obtained from the database of Gene Expression Omnibus. Using limma package, the differentially expressed genes (DEGs) between samples from AD and healthy control were selected. Furthermore, function analysis was conducted. Meanwhile, the protein-protein interaction (PPI) network and transcription factor (TF)-miRNA-target regulatory network were constructed. And quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expressions patterns of key genes.RESULTS: In total, 285 DEGs including 214 upregulated and 71 downregulated genes were identified between samples from two groups. The upregulated DEGs were mainly involved in nine pathways, such as hematopoietic cell lineage, pertussis, p53 signaling pathway, staphylococcus aureus infection, and cell cycle, while tight junction was the only pathway enriched by the downregulated DEGs. Cyclin B (CCNB)1, CCNB2, cyclin A (CCNA)2, C-X-C motif chemokine ligand (CXCL)10, and CXCL9 were key nodes in PPI network. The TF-miRNA-target gene regulatory network focused on miRNAs such as miR-106b, miR-106a, and miR-17, TFs such as nuclear factor kappa B subunit 1, RELA proto-oncogene, Sp1 transcription factor, and genes such as matrix metallopeptidase 9, peroxisome proliferator activated receptor gamma , and serpin family E member 1. Moreover, the upregulation of these genes, including CCNB1, CCNB2, CCNA2, CXCL10, and CXCL9 were confirmed by qRT-PCR.CONCLUSION: CCNB1, CCNB2, CCNA2, and CXCL9 might be novel markers of mild AD. miR-106b and miR-17 may involve in regulation of immune response in AD patients.


Subject(s)
Asian Continental Ancestry Group , Biomarkers , Cell Cycle , Cell Lineage , Computational Biology , Cyclin A , Cyclin B , Dataset , Dermatitis , Dermatitis, Atopic , Gene Expression , Gene Regulatory Networks , Humans , MicroRNAs , NF-kappa B , PPAR gamma , Proto-Oncogenes , Real-Time Polymerase Chain Reaction , Skin Diseases , Sp1 Transcription Factor , Staphylococcus aureus , Tight Junctions , Transcription Factors , Up-Regulation , Whooping Cough
7.
Article in Chinese | WPRIM | ID: wpr-774083

ABSTRACT

OBJECTIVE@#To study the effects of respiratory syncytial virus (RSV) infection on epidermal growth factor receptor (EGFR), tight junction association proteins and mucin in the human airway epithelial cells.@*METHODS@#Human airway epithelial cells NCI-H292 were randomly treated by ultraviolet light-inactivated RSV (control group) or thawed RSV (RSV infection group). After 48 hours of treatment, the protein levels of occludin, E-cadherin, phosphorylated EGFR and EGFR in NCI-H292 cells were measured by Western blot. The distribution and expression levels of occludin and E-cadherin in NCI-H292 cells were examined by immunofluorescence technique. The expression levels of MUC5AC mRNA in NCI-H292 cells were assessed by RT-PCR.@*RESULTS@#The protein levels of occludin and E-cadherin were significantly reduced in the RSV infection group compared with the control group (P<0.05). The protein levels of phosphorylated EGFR and EGFR increased significantly in the RSV infection group compared with the control group (P<0.05). The MUC5AC mRNA levels also increased significantly in the RSV infection group compared with the control group (P<0.05).@*CONCLUSIONS@#RSV may down-regulate the tight junction association proteins and up-regulate the expression of MUC5AC in airway epithelial cells, which contributes to epithelial barrier dysfunction. EGFR phosphorylation may play an important role in regulation of airway barrier.


Subject(s)
Cell Line , Epithelial Cells , ErbB Receptors , Humans , Mucin 5AC , Respiratory Syncytial Virus Infections , Tight Junction Proteins , Tight Junctions
8.
Chinese Journal of Biotechnology ; (12): 931-941, 2019.
Article in Chinese | WPRIM | ID: wpr-771833

ABSTRACT

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.


Subject(s)
Claudins , Therapeutic Uses , Enterotoxins , Humans , Neoplasms , Drug Therapy , Tight Junctions
9.
Article in English | WPRIM | ID: wpr-762138

ABSTRACT

PURPOSE: Protease-activated receptor 2 (PAR2) reportedly triggers the immune response in allergic asthma. We aimed to investigate the mechanism on allergic inflammation mediated by PAR2. METHODS: Human lung epithelial cells (A549 cells) were used for in vitro, and the German cockroach extract (GCE)-induced mouse model was developed for in vivo studies. RESULTS: In A549 cells, the levels of reactive oxygen species (ROS) and thymic stromal lymphopoietin (TSLP) were significantly increased by GCE treatment, but were suppressed by PAR2-antagonist (PAR2-ant) or N-acetylcysteine (NAC) treatment. Claudin-1 was degraded by GCE, and was restored by PAR2-ant or NAC in the cells. In the mouse model, the clinical appearance including bronchial hyperresponsiveness, bronchoalveolar lavage fluid analysis and total immunoglobulin E were significantly suppressed by PAR2-ant or NAC. Moreover, TSLP levels in the lung were suppressed by the same treatments in the lung. Claudin-1 was also degraded by GCE, and was restored by PAR2-ant or NAC. CONCLUSIONS: ROS generation and epidermal tight junction degradation are triggered by protease, followed by the induction of TSLP in allergic asthma. Our findings could suggest that PAR2-ant or anti-oxidants could be considered for allergic diseases as preventive alternatives.


Subject(s)
Acetylcysteine , Animals , Asthma , Blattellidae , Bronchoalveolar Lavage Fluid , Claudin-1 , Epithelial Cells , Humans , Immunoglobulin E , Immunoglobulins , In Vitro Techniques , Inflammation , Lung , Mice , Oxygen , Reactive Oxygen Species , Receptor, PAR-2 , Receptors, Proteinase-Activated , Tight Junctions
10.
Article in English | WPRIM | ID: wpr-741710

ABSTRACT

BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to 12.5–50 µg/mL extract. However, absence of XBP1 or IRE1α in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an IRE1α-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.


Subject(s)
Animals , Asia , Carrier Proteins , Cell Line , Diet , Endoplasmic Reticulum , Epithelial Cells , Fibroblasts , Fruit , Humans , Immunoglobulins , Inflammation , Inflammatory Bowel Diseases , Interleukin-6 , Interleukin-8 , Interleukins , Intestines , Lycium , Mice , Microscopy , Permeability , Tight Junctions
11.
Article in English | WPRIM | ID: wpr-739654

ABSTRACT

Intestinal barrier dysfunction always accompanies cirrhosis in patients with advanced liver disease and is an important contributor facilitating bacterial translocation (BT), which has been involved in the pathogenesis of cirrhosis and its complications. Several studies have demonstrated the protective effect of Vitamin D on intestinal barrier function. However, severe cholestasis leads to vitamin D depletion. This study was designed to test whether vitamin D therapy improves intestinal dysfunction in cirrhosis. Rats were subcutaneously injected with 50% sterile CCl₄ (a mixture of pure CCl₄ and olive oil, 0.3 mL/100 g) twice a week for 6 weeks. Next, 1,25(OH)₂D₃(0.5 µg/100 g) and the vehicle were administered simultaneously with CCl₄ to compare the extent of intestinal histologic damage, tight junction protein expression, intestinal barrier function, BT, intestinal proliferation, apoptosis, and enterocyte turnover. Intestinal heme oxygenase-1 (HO-1) expression and oxidative stress were also assessed. We found that vitamin D could maintain intestinal epithelial proliferation and turnover, inhibit intestinal epithelial apoptosis, alleviate structural damage, and prevent BT and intestinal barrier dysfunction. These were achieved partly through restoration of HO-1 and inhibition of oxidative stress. Taken together, our results suggest that vitamin D ameliorated intestinal epithelial turnover and improved the integrity and function of intestinal barrier in CCl₄-induced liver cirrhotic rats. HO-1 signaling activation was involved in these above beneficial effects.


Subject(s)
Animals , Apoptosis , Bacterial Translocation , Cholestasis , Enterocytes , Fibrosis , Heme Oxygenase-1 , Heme , Humans , Liver , Liver Diseases , Olive Oil , Oxidative Stress , Rats , Tight Junctions , Vitamin D , Vitamins
12.
Experimental Neurobiology ; : 216-228, 2019.
Article in English | WPRIM | ID: wpr-739543

ABSTRACT

The complement cascade is a central component of innate immunity which plays a critical role in brain inflammation. Complement C3a receptor (C3aR) is a key mediator of post-ischemic cerebral injury, and pharmacological antagonism of the C3a receptor is neuroprotective in stroke. Cerebral ischemia injures brain endothelial cells, causing blood brain barrier (BBB) disruption which further exacerbates ischemic neuronal injury. In this study, we used an in vitro model of ischemia (oxygen glucose deprivation; OGD) to investigate the protective effect of a C3aR antagonist (C3aRA, SB290157) on brain endothelial cells (bEnd.3). Following 24 hours of reperfusion, OGD-induced cell death was assessed by TUNEL and Caspase-3 staining. Western blot and immunocytochemistry were utilized to demonstrate that OGD upregulates inflammatory, oxidative stress and antioxidant markers (ICAM-1, Cox-2, Nox-2 and MnSOD) in endothelial cells and that C3aRA treatment significantly attenuate these markers. We also found that C3aRA administration restored the expression level of the tight junction protein occludin in endothelial cells following OGD. Interestingly, OGD/reperfusion injury increased the phosphorylation of ERK1/2 and C3aR inhibition significantly reduced the activation of ERK suggesting that endothelial C3aR may act via ERK signaling. Furthermore, exogenous C3a administration stimulates these same inflammatory mechanisms both with and without OGD, and C3aRA suppresses these C3a-mediated responses, supporting an antagonist role for C3aRA. Based on these results, we conclude that C3aRA administration attenuates inflammation, oxidative stress, ERK activation, and protects brain endothelial cells following experimental brain ischemia.


Subject(s)
Blood-Brain Barrier , Blotting, Western , Brain Ischemia , Brain , Caspase 3 , Cell Death , Complement C3a , Complement System Proteins , Encephalitis , Endothelial Cells , Glucose , Immunity, Innate , Immunohistochemistry , In Situ Nick-End Labeling , In Vitro Techniques , Inflammation , Ischemia , Neurons , Occludin , Oxidative Stress , Phosphorylation , Reperfusion , Stroke , Tight Junctions
13.
Article in Chinese | WPRIM | ID: wpr-776003

ABSTRACT

To investigate the expressions of mucosal barrier proteins in colon cell line DLD-1 under hypoxic environment and its mechanism. Methods After DLD-1 cells were treated separately with hypoxia(l% O),vitamin D(100 nmol/L),or vitamin D plus hypoxia for 48 hours,the expressions of vitamin D receptor(VDR),tight junction proteins zonula occludens-1(ZO-1),occludin,Claudin-1,and adherent junction protein(E-cadherin)were determined by Western blot.Stable VDR knock-down(Sh-VDR)DLD-1 cell line and control DLD-1 cell line were established by lentivirus package technology and the protein expressions after hypoxia treatment were detected. Results Compared with control group,the expressions of occludin,Claudin-1,and VDR increased significantly after hypoxia treatment(all <0.001).In addition to the protein expressions of occludin,Claudin-1 and VDR,the expressions of ZO-1 and E-cadherin were also obviously higher in vitamin D plus hypoxia group than in single vitamin D treatment group(all <0.001).After hypoxia treatment,Sh-VDR cell line showed significantly decreased expressions of ZO-1(<0.001),occludin(<0.05),Claudin-1(<0.01)and E-cadherin(<0.001)when compared with untreated Sh-VDR cell line. Conclusion VDR acts as a regulator for the expressions of intestinal mucosal barrier proteins under hypoxia environment in DLD-1 colon cell line,indicating that VDR pathway may be another important protective mechanism for gut barrier in low-oxygen environment.


Subject(s)
Antigens, CD , Metabolism , Cadherins , Metabolism , Cell Hypoxia , Cell Line , Claudin-1 , Metabolism , Colon , Cell Biology , Humans , Occludin , Metabolism , Receptors, Calcitriol , Metabolism , Tight Junctions , Vitamin D , Pharmacology , Zonula Occludens-1 Protein , Metabolism
14.
Article in Chinese | WPRIM | ID: wpr-775043

ABSTRACT

OBJECTIVE@#To establish a congenital chloride diarrhea (CCD)-associated SLC26A3 c.392C>G (p.P131R) polymorphism-expressing cell model, and to investigate its biological function.@*METHODS@#The sequence of the SLC26A3 gene in GenBank was used to design the upstream and downstream single-guide RNA (sgRNA) that could specifically recognize the 392 locus of the SLC26A3 gene, and the sgRNA was mixed with the pSpCas9-puro vector after enzyme digestion to construct an eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3). Caco-2 cells were transfected with the recombinant plasmid and synthesized single-stranded DNA oligonucleotides (ssODNs), and Taqman genotyping assay and Sanger sequencing were used to identify the expression of SLC26A3 c.392C>G (p.P131R) in Caco-2 cells. Wild-type Caco-2 cells were selected as normal control group and the Caco-2 cells with successful expression of SLC26A3 c.392C>G (p.P131R) was selected as P131R group. Both groups were treated with 100 ng/mL tumor necrosis factor-α (TNF-α), and then the normal control group was named as TNF-α group, and the P131R group was named as TNF-α+P131R group. Electric cell-substrate impedance sensing (ECIS) assay was used to evaluate the change in the monolayer barrier function of intestinal epithelial cells in the above four groups, and Western blot was used to measure the change in the expression of SLC26A3 protein in the normal control group and the P131R group.@*RESULTS@#The eukaryotic recombinant expression plasmid (pSpCas9-SLC26A3) was successfully constructed. Both Taqman genotyping assay and Sanger sequencing confirmed the successful establishment of the Caco-2 cell model of SLC26A3 c.392C>G (p.P131R) expression. ECIS assay showed that compared with the normal control group, the P131R group had a significant increase in the monolayer permeability of intestinal epithelial cells (PG (p.P131R) can reduce the expression of SLC26A3 protein, increase the monolayer permeability of intestinal epithelial cells, and thus lead to diarrhea.


Subject(s)
Caco-2 Cells , Chloride-Bicarbonate Antiporters , Genetics , Diarrhea , Genetics , Humans , Intestinal Mucosa , Metabolism, Inborn Errors , Genetics , Polymorphism, Single Nucleotide , Sulfate Transporters , Genetics , Tight Junctions , Tumor Necrosis Factor-alpha
15.
Article in English | WPRIM | ID: wpr-764212

ABSTRACT

BACKGROUND AND OBJECTIVES: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Despite its desirable effect, HPβCD can induce hearing loss, which is the only major side effect noted to date. Understanding of the pathophysiology of hearing impairment after administration of HPβCD and further development of preventive methods are essential to reduce the ototoxic side effect. The mechanisms of HPβCD-induced ototoxicity remain unknown, but the resulting pathology bears some resemblance to other ototoxic agents, which involves oxidative stress pathways. To indirectly determine the involvement of oxidative stress in HPβCD-induced ototoxicity, we tested the efficacy of an antioxidant reagent, ebselen, on the extent of inner ear side effects caused by HPβCD. MATERIALS AND METHODS: Ebselen was applied prior to administration of HPβCD in mice. Auditory brainstem response thresholds and otopathology were assessed one week later. Bilateral effects of the drug treatments also were examined. RESULTS: HPβCD-alone resulted in bilateral, severe, and selective loss of outer hair cells from base to apex with an abrupt transition between lesions and intact areas. Ebselen co-treatment did not ameliorate HPβCD-induced hearing loss or alter the resulting histopathology. CONCLUSIONS: The results indirectly suggest that cochlear damage by HPβCD is unrelated to reactive oxygen species formation. However, further research into the mechanism(s) of HPβCD otopathology is necessary.


Subject(s)
Animals , Ear, Inner , Evoked Potentials, Auditory, Brain Stem , Hair Cells, Auditory, Outer , Hearing Loss , Hearing , Humans , Mice , Oxidative Stress , Pathology , Reactive Oxygen Species , Sphingolipidoses , Tight Junctions
16.
J. health med. sci. (Print) ; 4(1): 17-21, Ene.-Mar. 2018.
Article in Spanish | LILACS | ID: biblio-1151482

ABSTRACT

El objetivo de esta revisión fue exponer el conocimiento actual sobre la relación existente entre dietas altas en grasa (DAG), alteraciones morfológicas de la mucosa intestinal, efectos inflamatorios y cáncer intestinal. Las DAG inicialmente producen aumento de la microbiota patógena, lo que reduce la cantidad y calidad de la secreción de los exocrinocitos caliciformes, disminuyendo la efectividad de la barrera intestinal. Las bacterias y sus lipopolisacaridos (LPS) promueven la secreción de citoquinas proinflamatorias activando vías de inflamación, que a su vez afectan la integridad de las uniones intercelulares alterando la barrera intestinal. Lo anterior, permite que los LPS ingresen a la lámina propia y circulación sanguínea produciendo inflamación local y sistémica. Así mismo, las DAG generan efectos nocivos en la morfología y función de la mucosa gastrointestinal lo que podría favorecer el desarrollo de cáncer. Lo anterior, podría deberse a que el consumo de DAG es capaz de aumentar la proliferación de células de la mucosa y el número y proliferación de células madres tumorales en el intestino.


The aim of this review was to present current knowledge about the relationship between high fat diets (HFD), morphological alterations of intestinal mucosa, inflammatory effects and intestinal cancer. The HFD initially produces an increase in the pathogenic microbiota, which reduces quantity and quality of secretion of goblet cells, decreasing the effectiveness of intestinal barrier. Bacteria and their lipopolysaccharides (LPS) stimulate the secretion of proinflammatory cytokines by activating inflammation pathways, which in turn affect the integrity of intercellular junctions by changing intestinal barrier. The above allows the LPS enter to lamina propria and blood circulation producing local and systemic inflammation. Likewise, HFD generate deleterious effects on morphology and function of gastrointestinal mucosa, which could favor the development of cancer. This could be due to the fact that consumption of HFD is capable of increasing proliferation of mucosal cells and number and proliferation of tumor stem cells in the intestine.


Subject(s)
Humans , Dietary Fats/adverse effects , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome/drug effects , Inflammation/etiology , Intestinal Mucosa/drug effects , Bile Acids and Salts/metabolism , Cytokines/metabolism , Tight Junctions/drug effects , Gastrointestinal Tract/microbiology , Inflammation/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology
17.
Article in English | WPRIM | ID: wpr-766076

ABSTRACT

PURPOSE: Epithelial barrier dysfunction is involved in the pathophysiology of periodontitis and oral lichen planus. Estrogens have been shown to enhance the physical barrier function of intestinal and esophageal epithelia, and we aimed to investigate the effect of estradiol (E2) on the regulation of physical barrier and tight junction (TJ) proteins in human oral epithelial cell monolayers. METHODS: HOK-16B cell monolayers cultured on transwells were treated with E2, an estrogen receptor (ER) antagonist (ICI 182,780), tumor necrosis factor alpha (TNFα), or dexamethasone (Dexa), and the transepithelial electrical resistance (TER) was then measured. Cell proliferation was measured by the cell counting kit (CCK)-8 assay. The levels of TJ proteins and nuclear translocation of nuclear factor (NF)-κB were examined by confocal microscopy. RESULTS: E2 treatment increased the TER and the levels of junctional adhesion molecule (JAM)-A and zonula occludens (ZO)-1 in a dose-dependent manner, without affecting cell proliferation during barrier formation. Treatment of the tight-junctioned cell monolayers with TNFα induced decreases in the TER and the levels of ZO-1 and nuclear translocation of NF-κB. These TNFα-induced changes were inhibited by E2, and this effect was completely reversed by co-treatment with ICI 182,780. Furthermore, E2 and Dexa presented an additive effect on the epithelial barrier function. CONCLUSIONS: E2 reinforces the physical barrier of oral epithelial cells through the nuclear ER-dependent upregulation of TJ proteins. The protective effect of E2 on the TNFα-induced impairment of the epithelial barrier and its additive effect with Dexa suggest its potential use to treat oral inflammatory diseases involving epithelial barrier dysfunction.


Subject(s)
Architectural Accessibility , Cell Count , Cell Proliferation , Dexamethasone , Electric Impedance , Epithelial Cells , Estradiol , Estrogens , Humans , Junctional Adhesion Molecule A , Junctional Adhesion Molecules , Lichen Planus, Oral , Microscopy, Confocal , NF-kappa B , Periodontitis , Tight Junctions , Tumor Necrosis Factor-alpha , Up-Regulation
18.
Yonsei Medical Journal ; : 1222-1231, 2018.
Article in English | WPRIM | ID: wpr-719241

ABSTRACT

PURPOSE: Cockroach exposure is a pivotal cause of asthma. Tight junctions are intercellular structures required for maintenance of the barrier function of the airway epithelium, which is impaired in this disease. Matrix metalloproteinases (MMPs) digest extracellular matrix components and are involved in asthma pathogenesis: MMP1 is a collagenase with a direct influence on airway obstruction in asthmatics. This study aimed to investigate the mechanism by which German cockroach extract (GCE) induces MMP1 expression and whether MMP1 release alters cellular tight junctions in human airway epithelial cells (NCI-H292). MATERIALS AND METHODS: mRNA and protein levels were determined using real-time PCR and ELISA. Tight junction proteins were detected using immunofluorescence staining. Epithelial barrier function was measured by transepithelial electrical resistance (TEER). The binding of a transcription factor to DNA molecules was determined by electrophoretic mobility shift assay, while the levels of tight junction proteins and phosphorylation were determined using Western blotting. RESULTS: GCE was shown to increase MMP1 expression, TEER, and tight junction degradation. Both an inhibitor and small interfering RNA (siRNA) of MMP1 significantly decreased GCE-induced tight junction disruption. Furthermore, transient transfection with ETS1 and SP1 siRNA, and anti-TLR2 antibody pretreatment prevented MMP1 expression and tight junction degradation. An extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) inhibitor also blocked MMP1 release, ETS1/SP1 DNA binding, and tight junction alteration. CONCLUSION: GCE treatment increases MMP1 expression, leading to tight junction disruption, which is transcriptionally regulated and influenced by the ERK/MAPK pathway in airway epithelial cells. These findings may contribute to developing novel therapeutic strategies for airway diseases.


Subject(s)
Airway Obstruction , Asthma , Blattellidae , Blotting, Western , Cockroaches , Collagenases , DNA , Electric Impedance , Electrophoretic Mobility Shift Assay , Enzyme-Linked Immunosorbent Assay , Epithelial Cells , Epithelium , Extracellular Matrix , Fluorescent Antibody Technique , Humans , Matrix Metalloproteinase 1 , Matrix Metalloproteinases , Phosphorylation , Phosphotransferases , Protein Kinases , Real-Time Polymerase Chain Reaction , RNA, Messenger , RNA, Small Interfering , Tight Junction Proteins , Tight Junctions , Transcription Factors , Transfection
19.
Article in English | WPRIM | ID: wpr-716678

ABSTRACT

PURPOSE: The tight junction protein claudin-5 (CLDN5) is critical to the control of endothelial cellular polarity and pericellular permeability. The role of CLDN5 in chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the association between CLDN5 levels and clinical variables in patients with COPD. METHODS: In total, 30 patients with COPD and 30 healthy controls were enrolled in the study. The plasma CLDN5 level was checked in patients with stable or exacerbated COPD and in healthy controls. RESULTS: The mean plasma CLDN5 level of patients with COPD was 0.63 ± 0.05 ng/mL and that of healthy controls was 6.9 ± 0.78 ng/mL (P = 0.001). The mean plasma CLDN5 level was 0.71 ± 0.05 ng/mL in exacerbated COPD patients and 0.63 ± 0.04 ng/mL in patients with stable COPD (P < 0.05). The plasma CLDN5 level among COPD subjects was correlated with the smoking amount (r = −0.530, P = 0.001). The plasma CLDN5 level in stable COPD patients was correlated with forced expiratory volume in one second (FEV1, %pred.) (r = −0.481, P = 0.037). CONCLUSIONS: The plasma CLDN5 level was not correlated with age. CLDN5 may be involved in the pathogenesis of COPD. Further studies having a larger sample size will be needed to clarify CLDN5 in COPD.


Subject(s)
Claudin-5 , Forced Expiratory Volume , Humans , Permeability , Plasma , Pulmonary Disease, Chronic Obstructive , Sample Size , Smoke , Smoking , Tight Junctions
20.
Gut and Liver ; : 411-419, 2018.
Article in English | WPRIM | ID: wpr-715591

ABSTRACT

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.


Subject(s)
Claudin-1 , Claudin-4 , Female , Fluconazole , Gastroesophageal Reflux , Hand , Humans , Male , Occludin , Polymerase Chain Reaction , Quality of Life , Receptors, Neurokinin-1 , RNA, Messenger , Tight Junction Proteins , Tight Junctions
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