• cancer
• cell migration
• cell proliferation
• claudin‐2
• inflammation
• tight junction

• 2308085J28 Natural Science Foundation of Anhui Province
• 2023AH020034 Natural Science Foundation of Anhui Province
• 82270623 National Natural Science Foundation of China
• 822250008 National Natural Science Foundation of China
• 82200644 National Natural Science Foundation of China
• 2070608 National Natural Science Foundation of China
• 82270589 National Natural Science Foundation of China

• Female
• Humans
• Ovarian Neoplasms/drug therapy
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/pathology
• Ovarian Neoplasms/genetics
• Animals
• Colforsin/pharmacology
• Cell Line, Tumor
• Mice
• Cisplatin/pharmacology
• Cystadenocarcinoma, Serous/drug therapy
• Cystadenocarcinoma, Serous/pathology
• Cystadenocarcinoma, Serous/metabolism
• Cystadenocarcinoma, Serous/genetics
• Proto-Oncogene Proteins c-myc/metabolism
• Proto-Oncogene Proteins c-myc/genetics
• Drug Repositioning
• Xenograft Model Antitumor Assays
• Apoptosis/drug effects
• Antineoplastic Agents/pharmacology
• Cell Proliferation/drug effects

• P50 CA228991 NCI NIH HHS

• Tight Junctions/metabolism
• Animals
• Humans
• Claudins/metabolism
• Claudins/chemistry
• Claudins/genetics

• R01 GM116961 NIGMS NIH HHS

• Cancer
• Claudin-12
• cell polarity
• metastasis
• paracellular permeability

• Duodenal mucosal expression
• Functional dyspepsia
• Meta-analysis
• Systematic review
• Tight junction proteins

• Oligopeptides/metabolism
• Oligopeptides/pharmacology
• Oligopeptides/pharmacokinetics
• Intestinal Absorption
• Humans
• Tight Junctions/metabolism
• Animals
• Biological Transport
• Intestinal Mucosa/metabolism
• Tight Junction Proteins/metabolism

• cell membrane
• glycolipid
• glycosylphosphatidylinositol
• interaction
• labelling
• photoaffinity
• proteomics

• Glycosylphosphatidylinositols/chemistry
• Cell Membrane/metabolism
• Polysaccharides/metabolism
• Membrane Proteins/metabolism
• Signal Transduction

• S10 OD030250 NIH HHS
• S10 OD021758 NIH HHS
• R35 GM131686 NIGMS NIH HHS
• S10 OD030250 ODCDC CDC HHS
• GM131686 NIGMS NIH HHS
• S10 OD021758 ODCDC CDC HHS

• CLDN1
• Claudins
• Hepatocellular Carcinoma

• Humans
• Carcinoma, Hepatocellular/pathology
• Claudin-1/metabolism
• Liver Neoplasms/pathology
• Claudins/metabolism
• Tight Junctions/metabolism

• endothelium
• epithelium
• paracellular permeability
• saliva secretion
• salivary gland
• tight junction

• Mice
• Animals
• Humans
• Tight Junctions/metabolism
• Tight Junctions/pathology
• Sjogren's Syndrome/pathology
• Endothelial Cells
• Salivary Glands/pathology
• Saliva/metabolism
• Submandibular Gland/metabolism
• Sialorrhea

• National Natural Science Foundation of China

• Autophagy
• Enteropathy
• Malnutrition
• Mitochondria
• SIRT1

• GPI-interacting protein
• alkyne
• diazirine
• glycosylphosphatidylinositol (GPI)
• photoactivated cross-linking
• proteomics

• Humans
• Glycosylphosphatidylinositols/analysis
• Glycosylphosphatidylinositols/chemistry
• Glycosylphosphatidylinositols/metabolism
• HeLa Cells
• Cell Membrane/chemistry
• Membrane Proteins/metabolism

• R35 GM131686 NIGMS NIH HHS
• S10 OD028753 NIH HHS

• Chemoresistance
• Metastasis
• Therapeutics
• Tight junctions
• Tumorigenesis

The claudin18.2 (CLDN18.2) protein, an isoform of claudin18, a member of the tight junction protein family, is a highly selective biomarker with limited expression in normal tissues and often abnormal expression during the occurrence and development of various primary malignant tumors, such as gastric cancer/gastroesophageal junction (GC/GEJ) cancer, breast cancer, colon cancer, liver cancer, head and neck cancer, bronchial cancer and non-small-cell lung cancer. CLDN18.2 participates in the proliferation, differentiation and migration of tumor cells. Recent studies have identified CLDN18.2 expression as a potential specific marker for the diagnosis and treatment of these tumors. With its specific expression pattern, CLDN18.2 has become a unique molecule for targeted therapy in different cancers, especially in GC; for example, agents such as zolbetuximab (claudiximab, IMAB362), a monoclonal antibody (mAb) against CLDN18.2, have been developed. In this review, we outline recent advances in the development of immunotherapy strategies targeting CLDN18.2, including monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), chimeric antigen receptor T (CAR-T) cells redirected to target CLDN18.2, and antibody–drug conjugates (ADCs).

• Antibody–drug conjugates (ADCs)
• Bispecific antibody (BsAb)
• Chimeric antigen receptor T (CAR-T) cells
• Claudin18.2
• Clinical trial
• Immunotherapy
• Molecular biomarker
• Monoclonal antibody (mAb)

Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer deaths worldwide, with a high frequency of recurrence and metastasis, and a poor prognosis. This review presents novel biological and clinical significance of claudin (CLDN) expression in GC, especially CLDN18, and clinical trials centered around CLDN18.2. It also presents new findings for other CLDNs.

Despite recent improvements in diagnostic ability and treatment strategies, advanced gastric cancer (GC) has a high frequency of recurrence and metastasis, with poor prognosis. To improve the treatment results of GC, the search for new treatment targets from proteins related to epithelial–mesenchymal transition (EMT) and cell–cell adhesion is currently being conducted. EMT plays an important role in cancer metastasis and is initiated by the loss of cell–cell adhesion, such as tight junctions (TJs), adherens junctions, desmosomes, and gap junctions. Among these, claudins (CLDNs) are highly expressed in some cancers, including GC. Abnormal expression of CLDN1, CLDN2, CLDN3, CLDN4, CLDN6, CLDN7, CLDN10, CLDN11, CLDN14, CLDN17, CLDN18, and CLDN23 have been reported. Among these, CLDN18 is of particular interest. In The Cancer Genome Atlas, GC was classified into four new molecular subtypes, and CLDN18–ARHGAP fusion was observed in the genomically stable type. An anti-CLDN18.2 antibody drug was recently developed as a therapeutic drug for GC, and the results of clinical trials are highly predictable. Thus, CLDNs are highly expressed in GC as TJs and are expected targets for new antibody drugs. Herein, we review the literature on CLDNs, focusing on CLDN18 in GC.

• CLDN18
• claudin
• gastric cancer
• metastasis

• Leak Pathway
• Pore Pathway
• ZO-1
• ZO-2
• claudin
• occludin
• paracellular permeability
• tight junction

• Animals
• Claudins/metabolism
• Epithelial Cells/metabolism
• Epithelial Cells/physiology
• Humans
• Occludin/metabolism
• Permeability
• Tight Junctions/metabolism
• Tight Junctions/physiology
• Zonula Occludens-1 Protein/metabolism
• Zonula Occludens-2 Protein/metabolism

• Claudin-5
• Hypoxia/reoxygenation
• Mirochondrial fragmentation
• Mitochondrial dynamics
• Myocardial ischemia/reperfusion

• CREB
• Cancer
• PKA
• cAMP

Stress-related mucosal disease (SRMD) is a common complication in patients in the intensive care unit (ICU). The aim of the present study was to investigate the possible mechanisms for the pathogenesis of SRMD. In total, 38 patients with SRMD were enrolled from an ICU, as well as 15 healthy volunteers. The disease severity of patients in ICU was evaluated using the Acute Physiology and Chronic Health Evaluation (APACHE) II score. Gastric mucosa with the most severe lesions were biopsied for hematoxylin and eosin staining and then assessed by pathological damage scoring. The serum levels of malondialdehyde (MDA), superoxide dismutase (SOD) and ischemic modified albumin (IMA) were also detected. In addition, claudin-3 and inducible nitric oxide (NO) synthase (iNOS) in the gastric mucosa were assessed by western blotting and immunohistochemistry. The average APACHE II score of the patients with SRMD was significantly higher compared with the controls. Moreover, the levels of MDA (4.74±2.89 nmol/ml) and IMA (93.61±10.78 U/ml) in patients with SRMD were significantly higher compared with the controls (P<0.001), while those of SOD (89.66±12.85 U/ml) in the patients with SRMD were significantly lower compared with the controls (P<0.001). Furthermore, compared with the control, iNOS expression was significantly higher (P=0.034), while the expression of claudin-3 was significantly lower in patients with SRMD (P<0.001). The results indicated that APACHE II score was positively correlated with pathological damage score (r=0.639, P<0.001) and levels of MDA (r=0.743, P<0.001), but negatively correlated with the level of SOD (r=-0.392, P=0.015). In addition, MDA was positively correlated with IMA (r=0.380, P=0.018), but negatively correlated with claudin-3 (r=-0.377, P=0.020). Therefore, it was speculated that oxidative stress may play an important role in the pathogenesis of SRMD, and NO levels and cell membrane permeability are altered during this process.

• Acute Physiology and Chronic Health Evaluation II score
• inducible NO synthase
• malondialdehyde
• oxidative stress
• stress-related mucosal disease

• Cancer progression
• Claudin-3
• Membrane localization
• Ovarian cancer
• S-Palmitoylation
• ZDHHC12

Epidermodysplasia verruciformis (EV) is a genodermatosis related to human beta-papillomavirus (beta-HPV), with a high risk of cutaneous squamous cell carcinoma (cSCC). Claudins are transmembrane proteins expressed in epithelia and may be altered during carcinogenesis. For a better understanding of the role of beta-HPV in cutaneous carcinogenesis, this claudin expression study was conducted on lesions of patients with and without EV. In this study, claudins-1, -2, -3, -4, -5, -7 and -11 expressions were analyzed by applying the immunohistochemistry technique, in samples of 108 normal skin, 39 flat warts and 174 cSCC. The cSCC samples were organized in tissue microarrays. We found that claudin-1 and claudin-3 focal expressions were associated with cSCC (p < 0.001), and claudin-2 focal or negative expression with flat wart (p < 0.001), in EV and NEV (non-EV) groups. For claudin-5, EV group showed a lower chance of focal and negative expression (p < 0.001), and its negative expression was associated with flat wart (p < 0.001) and lower mean age (p < 0.001). Claudins-4, -7 and -11 showed a diffuse expression in almost all studied samples. Our findings suggest that claudin-5 increased expression observed on normal skin, flat wart and cSCC showed association with EV. Claudin-1 and -3 down expression were also observed, but they could not be related to beta-HPV infection.

• caveolae
• clathrin
• endocytosis
• gut permeability
• tight junction

• Barrier function
• Cell-cell contact
• Claudin
• Junctional adhesion molecule
• LSR/angulin
• Occludin
• Permeability
• Post-translational modification
• Tight junction
• Transepithelial resistance
• Tricellulin

Claudins are cell–cell adhesion proteins, which are expressed in tight junctions (TJs), the most common apical cell-cell adhesion. Claudin proteins help to regulate defense and barrier functions, as well as differentiation and polarity in epithelial and endothelial cells. A series of studies have now reported dysregulation of claudin proteins in cancers. However, the precise mechanisms are still not well understood. Nonetheless, studies have clearly demonstrated a causal role of multiple claudins in the regulation of epithelial to mesenchymal transition (EMT), a key feature in the acquisition of a cancer stem cell phenotype in cancer cells. In addition, claudin proteins are known to modulate therapy resistance in cancer cells, a feature associated with cancer stem cells. In this review, we have focused primarily on highlighting the causal link between claudins, cancer stem cells, and therapy resistance. We have also contemplated the significance of claudins as novel targets in improving the efficacy of cancer therapy. Overall, this review provides a much-needed understanding of the emerging role of claudin proteins in cancer malignancy and therapeutic management.

• cancer
• chemoresistance
• claudins
• stem cell

Recent studies have demonstrated that microRNA-155-5p (miR-155-5p) plays an essential role in the regulation of allergen-induced inflammation and is overexpressed in the skin of patients with atopic dermatitis (AD), although the mechanism is unknown. In this study, silencing miR-155-5p attenuated the thickening of the epidermis in AD model and reduced the infiltration of inflammatory cells and the secretion of Th2 cytokines. Protein kinase inhibitor α (PKIα) was identified as a direct target of miR-155-5p and correlated negatively with miR-155-5p in our AD model. Fluorescence in situ hybridization showed that miR-155-5p-expressing cells were predominantly present in the epidermis. When epithelial cells were transfected with an miR-155-5p inhibitor, the expression of PKIα, occludin, and CLDN16 increased and that of TSLP decreased significantly, whereas the overexpression of miR-155-5p resulted in the opposite changes. The increased expression of PKIα and tight junction (TJ) proteins, with reduced TSLP and IL-33, was also detected in miR-155-5p-blocked mice, in both the initial and elicitation stages of AD. The expression of TJ proteins also decreased when cells were transfected with PKIα siRNA. TJ proteins increased and TSLP and IL-33 decreased significantly after the overexpression of PKIα. Our data provide the first evidence that miR-155-5p is critical for the allergic inflammation in a mouse model of AD by directly regulating PKIα and thus epithelial TJ expression. These findings suggest new therapeutic strategies that target miR-155-5p in patients with allergic disorders.

• Barrier function
• Blood-brain barrier
• Claudin
• Endothelial cell
• Endothelium
• Occludin
• Tight junction
• Vascular homeostasis
• Zonula occludens

Claudin-1 (CLDN1) is expressed in the tight junction (TJ) of the skin granular layer and acts as a physiological barrier for the paracellular transport of ions and nonionic molecules. Ultraviolet (UV) and oxidative stress may disrupt the TJ barrier, but the mechanism of and protective agents against this effect have not been clarified. We found that UVB and hydrogen peroxide (H₂O₂) caused the internalization of CLDN1 and increased the paracellular permeability of lucifer yellow, a fluorescent marker, in human keratinocyte-derived HaCaT cells. Therefore, the mechanism of mislocalization of CLDN1 and the protective effect of an ethanol extract of Brazilian green propolis (EBGP) were investigated. The UVB- and H₂O₂-induced decreases in CLDN1 localization were rescued by EBGP. H₂O₂ decreased the phosphorylation level of CLDN1, which was also rescued by EBGP. Wild-type CLDN1 was distributed in the cytosol after treatment with H₂O₂, whereas T191E, its H₂O₂-insensitive phosphorylation-mimicking mutant, was localized at the TJ. Both protein kinase C activator and protein phosphatase 2A inhibitor rescued the H₂O₂-induced decrease in CLDN1 localization. The tight junctional localization of CLDN1 and paracellular permeability showed a negative correlation. Our results indicate that UVB and H₂O₂ could induce the elevation of paracellular permeability mediated by the dephosphorylation and mislocalization of CLDN1 in HaCaT cells, which was rescued by EBGP. EBGP and its components may be useful in preventing the destruction of the TJ barrier through UV and oxidative stress.

• claudin-1
• hydrogen peroxide
• phosphorylation

• IPEC-J2
• N-Acetyl-D-Galactosamine
• SBA
• mechanical barrier
• membrane permeability
• tight junctions

• Acetylgalactosamine/administration & dosage
• Acetylgalactosamine/pharmacology
• Agglutinins/pharmacology
• Agglutinins/toxicity
• Alkaline Phosphatase/genetics
• Alkaline Phosphatase/metabolism
• Animals
• Cell Line
• Cell Membrane/drug effects
• Epithelial Cells/drug effects
• Epithelial Cells/physiology
• Gene Expression Regulation, Enzymologic/drug effects
• Intestinal Mucosa/cytology
• Permeability
• RNA/genetics
• RNA/metabolism
• Glycine max/chemistry
• Swine

• (2017YFD0502004) national key research and development program of China
• (31201763) National Natural Science Foundation of China
• (20180101023JC) Scientific Project of Jilin Province
• (20170309003NY) Scientific Project of Jilin Province

• Na reabsorption
• cGMP
• kidney
• loop of Henle
• nitric oxide

• claudin-4
• homology modeling
• molecular dynamics
• virtual screening

• Claudin-10
• Janus kinase 1
• Metastasis
• Osteosarcoma
• Signal transducer and activator of transcription1

Tabariès et al. show that signaling downstream from a Claudin-2/Afadin complex enables the efficient formation of breast cancer metastases.

Claudin-2 promotes breast cancer liver metastasis by enabling seeding and early cancer cell survival. We now demonstrate that the PDZ-binding motif of Claudin-2 is necessary for anchorage-independent growth of cancer cells and is required for liver metastasis. Several PDZ domain-containing proteins were identified that interact with the PDZ-binding motif of Claudin-2 in liver metastatic breast cancer cells, including Afadin, Arhgap21, Pdlim2, Pdlim7, Rims2, Scrib, and ZO-1. We specifically examined the role of Afadin as a potential Claudin-2-interacting partner that promotes breast cancer liver metastasis. Afadin associates with Claudin-2, an interaction that requires the PDZ-binding motif of Claudin-2. Loss of Afadin also impairs the ability of breast cancer cells to form colonies in soft agar and metastasize to the lungs or liver. Immunohistochemical analysis of Claudin-2 and/or Afadin expression in 206 metastatic breast cancer tumors revealed that high levels of both Claudin-2 and Afadin in primary tumors were associated with poor disease-specific survival, relapse-free survival, lung-specific relapse, and liver-specific relapse. Our findings indicate that signaling downstream from a Claudin-2/Afadin complex enables the efficient formation of breast cancer metastases. Moreover, combining Claudin-2 and Afadin as prognostic markers better predicts the potential of breast cancer to metastasize to soft tissues.

• Afadin
• Claudin-2
• breast cancer
• liver metastasis
• lung metastasis

The ability of epithelial cells to organize through cell–cell adhesion into a functioning epithelium serves the purpose of a tight epithelial protective barrier. Contacts between adjacent cells are made up of tight junctions (TJ), adherens junctions (AJ), and desmosomes with unique cellular functions and a complex molecular composition. These proteins mediate firm mechanical stability, serves as a gatekeeper for the paracellular pathway, and helps in preserving tissue homeostasis. TJ proteins are involved in maintaining cell polarity, in establishing organ-specific apical domains and also in recruiting signaling proteins involved in the regulation of various important cellular functions including proliferation, differentiation, and migration. As a vital component of the epithelial barrier, TJs are under a constant threat from proinflammatory mediators, pathogenic viruses and bacteria, aiding inflammation and the development of disease. Inflammatory bowel disease (IBD) patients reveal loss of TJ barrier function, increased levels of proinflammatory cytokines, and immune dysregulation; yet, the relationship between these events is partly understood. Although TJ barrier defects are inadequate to cause experimental IBD, mucosal immune activation is changed in response to augmented epithelial permeability. Thus, the current studies suggest that altered barrier function may predispose or increase disease progression and therapies targeted to specifically restore the barrier function may provide a substitute or supplement to immunologic-based therapies. This review provides a brief introduction about the TJs, AJs, structure and function of TJ proteins. The link between TJ proteins and key signaling pathways in cell proliferation, transformation, and metastasis is discussed thoroughly. We also discuss the compromised intestinal TJ integrity under inflammatory conditions, and the signaling mechanisms involved that bridge inflammation and cancer.

• claudin
• metastasis
• signaling molecules
• tight junction
• tumor

A prior study by our group using cDNA array analysis identified the tight junction component claudin-12 (CLDN12) to be an upregulated gene in lung squamous cell carcinoma (SqCC) cells compared with normal human bronchial epithelial cells. The present study aimed to explore the effect and underlying molecular mechanism of CLDN12 with regard to the malignant phenotype of SqCC. Firstly, the expression patterns of CLDN12 in SqCC tissues, lung adenocarcinoma tissues and histologically non-neoplastic lung epithelial tissues were investigated by immunohistochemistry and western blotting. Additionally, associations between CLDN12 expression and clinicopathological indicators were examined in patients with SqCC. Furthermore, the impact of CLDN12 on the malignant phenotype of the human bronchial epithelial cell line BEAS-2B in vitro was assessed using the Cell Counting kit-8 assay, Transwell assay and a wound-healing experiment. Western blotting and immunofluorescence were also used to detect the impact of CLDN12 on the epithelial-mesenchymal transition (EMT) of BEAS-2B cells. Tyrosine kinase 2 (Tyk2) RNA interference was further utilized to determine the impact of the Tyk2/signal transducer and activator of transcription 1 (Stat1) signaling pathway on the EMT of BEAS-2B cells. To conclude, it was indicated that the expression of CLDN12 was upregulated in SqCC tissues and was associated with the extent of lymphatic metastasis in patients with SqCC. Furthermore, CLDN12 promoted the EMT of human bronchial epithelial cells in vitro. The findings indicated that the induction of Tyk2/Stat1 signaling appears to be an important mechanism by which CLDN12 promotes the EMT of SqCC cells.

• claudin-12
• epithelial-mesenchymal transition
• lung squamous cell carcinoma
• metastasis
• tight junction

In an earlier study, we investigated the expression of tight junction protein claudins (CLDNs) in human osteosarcoma (OS) cells, and the CLDN2 was found to be down-regulated in primary tumor cells compared with normal osteoblast cells. Here, we sought to explore the effects of CLDN2 on the malignant phenotype of OS and the underlying molecular mechanisms.

The expression patterns of CLDN2 and afadin in OS tissues and histologically non-neoplastic bone tissues were explored via immunohistochemistry and western blotting. CLDN2 expression levels in an OS cell line stably expressing CLDN2 and an osteoblast cell line with a CLDN2 knockout were confirmed by western blotting and immunofluorescence staining. The malignant phenotype of OS cells and osteoblast cells in vitro was assessed using a cell counting kit-8 assay, transwell assay and wound-healing experiment. Western blotting was utilized to detect the activation state of Ras/Raf/MEK/ERK pathway. Moreover, an RNA interference method were used to silence afadin in CLDN2-expressing OS cells.

Our research group found that CLDN2 and afadin was underexpressed in OS tissues, and the overexpression of CLDN2 significantly inhibited the migration abilities of OS cells. Genetic silencing of afadin in CLDN2-overexpressing OS cells promoted U2OS cell motility and activation of the Ras/Raf/MEK/ERK pathway.

In this study, we confirmed that CLDN2 expression significantly inhibited the malignant phenotype of OS cells in vitro. Inhibition of the ERK pathway by afadin may be one of the mechanisms by which CLDN2 blocks the metastasis phenotype of OS cells.

• Afadin
• Claudin-2
• Extracellular signal-regulated kinase
• Metastasis
• Osteosarcoma
• Tight junction

• BVES
• POPDC1
• POPEYE
• colitis-associated cancer

Hepatocellular carcinoma (HCC) is the second leading cause of cancer death in Asia; however, the molecular mechanism in its tumorigenesis remains unclear. Abnormal expression of claudins (CLDNs), a family of tight junction (TJ) proteins, plays an important role in the metastatic phenotype of epithelial-derived tumors by affecting tight junction structure, function and related cellular signaling pathways. In a previous study, we used a tissue chip assay to identify CLDN17 as an upregulated gene in HCC. Here we aimed to use molecular biology technology to explore the effect of CLDN17 on the malignant phenotype of HCC and the underlying molecular mechanism, with the objective of identifying a new target for HCC treatment and the control of HCC metastasis.

The expression levels of CLDN17 in HCC tissues and histologically non-neoplastic hepatic tissues were explored by immunohistochemistry. Stable transfection of the hepatocyte line HL7702 with CLDN17 was detected by real-time polymerase chain reaction (PCR), western blotting and immunofluorescence. The impact of CLDN17 on the malignant phenotype of HL7702 cells in vitro was assessed by a Cell Counting Kit-8 (CCK8) assay, a Transwell assay and a wound-healing experiment. Western blotting was utilized to detect the activation state of Tyrosine kinase 2 (Tyk2) / signal transducer and activator of transcription3 (Stat3) pathway. A Tyk2 RNA interference (RNAi) was utilized to determine the impact of the Tyk2/Stat3 signaling pathway on the malignant phenotype of hepatocytes.

In this work, our research group first found that CLDN17 was highly expressed in HCC tissues and was associated with poor prognosis. In addition, we demonstrated that CLDN17 affected the Stat3 signaling pathway via Tyk2 and ultimately enhanced the migration ability of hepatocytes.

In conclusion, we confirmed that the upregulated expression of CLDN17 significantly enhances the migration ability of hepatocytes in vitro and we found that the activation of the Stat3 pathway by Tyk2 may an important mechanism by which CLDN17 promotes aggressiveness in hepatocytes.

• CLDN17
• Hepatocytes
• Migration
• Signal transducer and activator of transcription 3
• Tight junction
• Tyrosine kinase 2

The main neurovascular unit of the Blood Brain Barrier (BBB) consists of a cellular component, which includes endothelial cells, astrocytes, pericytes, microglia, neurons, and oligodendrocytes as well as a non-cellular component resulting from the extracellular matrix. The endothelial cells are the major vital components of the BBB able to preserve the brain homeostasis. These cells are situated along the demarcation line between the bloodstream and the brain. Therefore, an alteration or the progressive disruption of the endothelial layer may clearly impair the brain homeostasis. The proper functioning of the brain endothelial cells is generally ensured by two elements: (1) the presence of junction proteins and (2) the preservation of a specific polarity involving an apical-luminal and a basolateral-abluminal membrane. This review intends to identify the molecular mechanisms underlying BBB function and their changes occurring in early stages of neurodegenerative processes in order to develop novel therapeutic strategies aimed to counteract neurodegenerative disorders.

• brain blood barrier
• endothelial dysfunction
• neurodegeneration

Numerous genetic alterations associated with cancer progression have the potential to serve as biomarkers for the early diagnosis of cancer. Numerous studies have suggested that claudin proteins, which are the primary components of tight junction structures, are associated with the regulation of cell polarity and cell differentiation. To investigate the expression profiles of the tight junction proteins claudin-2, −5, −7 and −8 in gastric carcinoma, immunohistochemical analysis, western blotting and reverse transcription-quantitative polymerase chain reaction analysis was used to detect the expression profiles of these claudin proteins in gastric carcinoma tissues and in homologous non-neoplastic mucosal tissues. According to the present study, the expression levels of claudin-7 and claudin-8 were downregulated, while the expression of claudin-5 was upregulated in gastric carcinoma tissues compared with in non-neoplastic mucosal tissues. Additionally, no notable difference was observed between claudin-2 expression in gastric carcinoma tissues and non-neoplastic mucosae. Correlations between claudin-7 and −8 expression and lymphatic metastasis in gastric carcinoma tissues were additionally reported. In summary, the present study revealed the distinct expression profiles of claudin-5, −7 and −8 in non-neoplastic mucosal tissues and gastric carcinoma tissues. Furthermore, the expression of these claudin proteins was highly associated with metastatic progression and prognosis in patients with gastric carcinoma, and had predictive value for the metastasis and survival of patients with gastric carcinoma.

• Adherens Junctions/physiology
• Animals
• Cell Movement
• Cell Proliferation
• Desmosomes/physiology
• Epithelial Cells/cytology
• Epithelial Cells/metabolism
• Epithelial Cells/ultrastructure
• Epithelium/metabolism
• Homeostasis
• Humans
• Intercellular Junctions/physiology
• Intestinal Mucosa/cytology
• Intestinal Mucosa/metabolism
• Intestinal Mucosa/physiology
• Signal Transduction
• Tight Junctions/physiology
• Wound Healing

• R35 GM118064 NIGMS NIH HHS
• T32 GM007276 NIGMS NIH HHS

• 3D culture
• CAPE
• Claudin-2
• Lung adenocarcinoma
• NF-κB

• A549 Cells
• Adenocarcinoma of Lung/drug therapy
• Adenocarcinoma of Lung/metabolism
• Caffeic Acids/chemistry
• Cantharidin/chemistry
• Cell Line, Tumor
• Cell Proliferation
• Chloroquine/chemistry
• Claudins/metabolism
• Down-Regulation
• Doxorubicin/chemistry
• Doxorubicin/pharmacology
• Drug Synergism
• Fatty Acids/chemistry
• Gene Expression Regulation
• Humans
• Lung Neoplasms/drug therapy
• Lung Neoplasms/metabolism
• Lysosomes/chemistry
• Permeability
• Phenylethyl Alcohol/analogs & derivatives
• Phenylethyl Alcohol/chemistry
• Promoter Regions, Genetic
• Propolis/chemistry
• RNA, Messenger/metabolism
• Tight Junctions

Several studies have suggested that claudin proteins, which are the main components of tight junction structures, are related to the regulation of cell polarity and cell differentiation.

To explore the expression profiles of the tight junction proteins claudin-2, − 5, − 8 and − 9 in nasopharyngeal carcinoma, IHC (immunohistochemical analysis), Western blot and real-time PCR were used to detect the expression profiles of these claudin proteins in nasopharyngeal carcinoma tissues and in non-neoplastic mucosal tissues.

According to our study, the expression levels of claudin-2 and claudin-5 were reduced, while the expression of claudin-8 was increased in nasopharyngeal carcinoma tissues in comparison with non-neoplastic mucosal tissues. Correlations between claudin-2 and -5 expression and metastatic progression in nasopharyngeal carcinoma patients were also found.

In summary, our research reveals distinct expression profiles of claudin-2, − 5 and − 8 in non-neoplastic mucosal tissues and nasopharyngeal carcinoma tissues. In addition, the expression of these claudin proteins was highly correlated with metastatic progression and prognosis in patients with nasopharyngeal carcinoma and had predictive value for the metastasis and survival of nasopharyngeal carcinoma patients.

• Claudin-2
• Claudin-5
• Claudin-8
• Claudin-9
• Nasopharyngeal carcinoma
• Tight junction

• JAM
• claudin
• occludin
• phosphorylation

• Claudin-1
• Claudin-3
• Claudin-4
• Claudin-7
• Claudin-8
• Extra-junctional claudin
• Infection
• Involution
• Mammary gland

• Animals
• Claudins/metabolism
• Epithelial Cells/cytology
• Epithelial Cells/metabolism
• Female
• Gene Expression Regulation, Developmental
• Lactation
• Mammary Glands, Animal/cytology
• Mammary Glands, Animal/metabolism
• Mice
• Mice, Inbred BALB C
• Pregnancy
• Tight Junctions/metabolism

• P01 HD038129 NICHD NIH HHS
• P30 CA046934 NCI NIH HHS
• R00 CA194318 NCI NIH HHS

Hearing and balance functions of the inner ear rely on the homeostasis of the endolymphatic fluid. When disturbed, pathologic endolymphatic hydrops evolves as observed in Menière’s disease. The molecular basis of inner ear fluid regulation across the endolymphatic epithelium is largely unknown. In this study we identified the specific expression of the tight junction (TJ) molecules Claudin 3, 4, 6, 7, 8, 10, and 16 in epithelial preparations of the rat inner ear endolymphatic duct (ED) and endolymphatic sac (ES) by high-throughput qPCR and immunofluorescence confocal microscopy. Further we showed that Claudin 4 in the ES is a target of arginine-vasopressin (AVP), a hormone elevated in Menière’s disease. Moreover, our transmission-electron microscopy (TEM) analysis revealed that the TJs of the ED were shallow and shorter compared to the TJ of the ES indicating facilitation of a paracellular fluid transport across the ED epithelium. The significant differences in the subcellular localization of the barrier-forming protein Claudin 3 between the ED and ES epithelium further support the TEM observations. Our results indicate a high relevance of Claudin 3 and Claudin 4 as important paracellular barrier molecules in the ED and ES epithelium with potential involvement in the pathophysiology of Menière’s disease.