Mikio Furuse

Kobe University, Kōbe, Hyōgo, Japan

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Publications (120)773.61 Total impact

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    ABSTRACT: Septate junctions (SJs) are membrane specializations that restrict the free diffusion of solutes via the paracellular pathway in invertebrate epithelia. In arthropods, two morphologically different types of SJs are observed: pleated SJs (pSJs) and smooth SJs (sSJs), which are present in ectodermally- and endodermally-derived epithelia, respectively. Recent identification of sSJ-specific proteins, Mesh and Ssk, in Drosophila indicates that the molecular compositions of sSJs and pSJs differ. A deficiency screen based on immunolocalization of Mesh, identified a tetraspanin family protein, Tsp2A, as a novel protein involved in sSJ formation in Drosophila. Tsp2A specifically localizes at sSJs in the midgut and Malpighian tubules. Compromised Tsp2A expression caused by RNAi or the CRISPR/Cas9 system was associated with defects in the ultrastructure of sSJs, changed localization of other sSJ proteins, and impaired barrier function of the midgut. In most Tsp2A-mutant cells, Mesh failed to localize to sSJs and was distributed through the cytoplasm. Tsp2A forms a complex with Mesh and Ssk and these proteins are mutually interdependent for their localization. These observations suggest that Tsp2A cooperates with Mesh and Ssk to organize sSJs.
    No preview · Article · Feb 2016 · Journal of Cell Science
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    ABSTRACT: The relationship between chronic inflammation and cancer is well known. The inflammation increases the permeability of blood vessels and consequently elevates pressure in the interstitial tissues. However, there have been only a few reports on the effects of hydrostatic pressure on cultured cells, and the relationship between elevated hydrostatic pressure and cell properties related to malignant tumors is less well understood. Therefore, we investigated the effects of hydrostatic pressure on the cultured epithelial cells seeded on permeable filters. Surprisingly, hydrostatic pressure from basal to apical side induced epithelial stratification in Madin-Darby canine kidney (MDCK) I and Caco-2 cells, and cavities with microvilli and tight junctions around their surfaces were formed within the multi-layered epithelia. The hydrostatic pressure gradient also promoted cell proliferation, suppressed cell apoptosis, and increased transepithelial ion permeability. The inhibition of protein kinase A (PKA) promoted epithelial stratification by the hydrostatic pressure whereas the activation of PKA led to suppressed epithelial stratification. These results indicate the role of the hydrostatic pressure gradient in the regulation of various epithelial cell functions. The findings in this study may provide clues for the development of a novel strategy for the treatment of the carcinoma.
    Preview · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: Tricellular tight junctions seal the extracellular spaces of tricellular contacts, where the vertices of three epithelial cells meet, and are required for the establishment of a strong barrier function of the epithelial cellular sheet. Angulins and tricellulin are known as specific protein components of tricellular tight junctions, where angulins recruit tricellulin. Mutations in the genes encoding angulin-2/ILDR1 and tricellulin have been reported to cause human hereditary deafness DFNB42 and DFNB49, respectively. To investigate the pathogenesis of DFNB42, we analyzed mice with a targeted disruption of Ildr1, which encodes angulin-2/ILDR1. Ildr1 null mice exhibited profound deafness. Hair cells in the cochlea of Ildr1 null mice develop normally, but begin to degenerate by two weeks after birth. Tricellulin localization at tricellular contacts of the organ of Corti in the cochlea was retained in Ildr1 null mice, but its distribution along the depth of tricellular contacts was affected. Interestingly, compensatory tricellular contact localization of angulin-1/LSR was observed in the organ of Corti in Ildr1 null mice although it was hardly detected in the organ of Corti in wild-type mice. The onset of hair cell degeneration in Ildr1 null mice was earlier than that in the reported Tric mutant mice, which mimic one of the tricellulin mutations in DFNB49 deafness. These results indicate that the angulin-2/ILDR1 deficiency causes the postnatal degenerative loss of hair cells in the cochlea, leading to human deafness DFNB42. Our data also suggest that angulin family proteins have distinct functions in addition to their common roles of tricellulin recruitment and that the function of angulin-2/ILDR1 for hearing cannot be substituted by angulin-1/LSR.
    Preview · Article · Mar 2015 · PLoS ONE
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    Shinsaku Tokuda · Mikio Furuse
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    ABSTRACT: Tight junctions (TJs) regulate the movements of substances through the paracellular pathway, and claudins are major determinants of TJ permeability. Claudin-2 forms high conductive cation pores in TJs. The suppression of claudin-2 expression by RNA interference in Madin-Darby canine kidney (MDCK) II cells (a low-resistance strain of MDCK cells) was shown to induce a three-fold increase in transepithelial electrical resistance (TER), which, however, was still lower than in high-resistance strains of MDCK cells. Because RNA interference-mediated knockdown is not complete and only reduces gene function, we considered the possibility that the remaining claudin-2 expression in the knockdown study caused the lower TER in claudin-2 knockdown cells. Therefore, we investigated the effects of claudin-2 knockout in MDCK II cells by establishing claudin-2 knockout clones using transcription activator-like effector nucleases (TALENs), a recently developed genome editing method for gene knockout. Surprisingly, claudin-2 knockout increased TER by more than 50-fold in MDCK II cells, and TER values in these cells (3000-4000 Ω·cm2) were comparable to those in the high-resistance strains of MDCK cells. Claudin-2 re-expression restored the TER of claudin-2 knockout cells dependent upon claudin-2 protein levels. In addition, we investigated the localization of claudin-1, -2, -3, -4, and -7 at TJs between control MDCK cells and their respective knockout cells using their TALENs. Claudin-2 and -7 were less efficiently localized at TJs between control and their knockout cells. Our results indicate that claudin-2 independently determines the 'leaky' property of TJs in MDCK II cells and suggest the importance of knockout analysis in cultured cells.
    Preview · Article · Mar 2015 · PLoS ONE
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    ABSTRACT: The immunoglobulin (Ig)-like domain containing receptor 1 (ILDR1) gene encodes angulin-2/ILDR1, a recently discovered tight junction protein, which forms tricellular tight junction (tTJ) structures with tricellulin and lipolysis-stimulated lipoprotein receptor (LSR) at tricellular contacts (TCs) in the inner ear. Previously reported recessive mutations within ILDR1 have been shown to cause severe to profound nonsyndromic sensorineural hearing loss (SNHL), DFNB42. Whole-exome sequencing of a Korean multiplex family segregating partial deafness identified a novel homozygous ILDR1 variant (p.P69H) within the Ig-like domain. To address the pathogenicity of p.P69H, the angulin-2/ILDR1 p.P69H variant protein, along with the previously reported pathogenic ILDR1 mutations, was expressed in angulin-1/LSR knockdown epithelial cells. Interestingly, partial mislocalization of the p.P69H variant protein and tricellulin at TCs was observed, in contrast to a severe mislocalization and complete failure of tricellulin recruitment of the other reported ILDR1 mutations. Additionally, three-dimensional protein modeling revealed that angulin-2/ILDR1 contributed to tTJ by forming a homo-trimer structure through its Ig-like domain, and the p.P69H variant was predicted to disturb homo-trimer formation. In this study, we propose a possible role of angulin-2/ILDR1 in tTJ formation in the inner ear and a wider audiologic phenotypic spectrum of DFNB42 caused by mutations within ILDR1.
    Preview · Article · Feb 2015 · PLoS ONE
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    ABSTRACT: The tight junction (TJ) barrier is located in the granular layer of the epidermis. Filaggrin deficiency predisposes patients to atopic dermatitis (AD) by impairing stratum corneum (SC) barrier function. Altered TJ barrier function has been observed in the skin of patients with AD; however, it remains unclear whether TJ function is influenced by filaggrin deficiency directly or secondarily via skin inflammation. To investigate the in vivo effects of filaggrin deficiency and skin inflammation on epidermal TJ function. Morphological changes in the TJ were investigated in filaggrin knockout mice and mice with hapten-induced dermatitis using en face visualization of epidermal sheets, and functional changes in the TJ were assessed with an in vivo permeation assay using tracers of various sizes. In filaggrin knockout mice, there was no apparent change in the honeycomb morphology of the TJ, TJ component mRNA expression, or TJ barrier function in neonates and adults, indicating that filaggrin-deficiency had no direct effects on the TJ. By contrast, in mice with hapten-induced dermatitis, the mRNA expression of TJ components was decreased markedly and the TJ barrier function was size-dependently impaired: the TJ leaked small tracers (<5kDa), but not large tracers (>30kDa). Filaggrin deficiency did not affect the epidermal TJ barrier directly, but once dermatitis occurred, the skin inflammation induced TJ dysfunction. Since TJ dysfunction induces the SC barrier impairment, skin inflammation will enhance skin permeability to external antigens and result in a vicious cycle of barrier dysfunction and skin inflammation. Copyright © 2014 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Nov 2014 · Journal of Dermatological Science
  • Yasushi Izumi · Mikio Furuse
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    ABSTRACT: Septate junctions (SJs) are specialized intercellular junctions that function as permeability barriers to restrict the free diffusion of solutes through the paracellular routes in invertebrate epithelia. SJs are subdivided into several morphological types that vary among different animal phyla. In several phyla, different types of SJ have been described in different epithelia within an individual. Arthropods have two types of SJs: pleated SJs (pSJs) and smooth SJs (sSJs), found in ectodermally and endodermally derived epithelia, respectively. Several lines of Drosophila research have identified and characterized a large number of pSJ-associated proteins. Two sSJ-specific proteins have been recently reported. Molecular dissection of SJs in Drosophila and animals in other phyla will lead to a better understanding of the functional differences among SJ types and of evolutionary aspects of these permeability barriers.
    No preview · Article · Sep 2014 · Seminars in Cell and Developmental Biology
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    Shinsaku Tokuda · Tomohito Higashi · Mikio Furuse
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    ABSTRACT: ZO-1, ZO-2 and ZO-3 are tight junction-associated scaffold proteins that bind to transmembrane proteins of tight junctions and the underlying cytoskeleton. ZO-1 is involved in the regulation of cytoskeletal organization, but its detailed molecular mechanism is less well understood. Gene knockout is an ideal method to investigate the functions of proteins that might have redundant functions such as ZO proteins, when compared with methods such as RNA interference-mediated suppression of gene expression. In this study we applied transcription activator-like effector nucleases (TALENs), a recently developed genome editing method for gene knockout, and established ZO-1 knockout clones in Madin-Darby canine kidney (MDCK) cells. ZO-1 knockout induced striking changes in myosin organization at cell-cell contacts and disrupted the localization of tight junction proteins; these findings were previously unseen in studies of ZO-1 knockdown by RNA interference. Rescue experiments revealed that trace ZO-1 expression reversed these changes while excessive ZO-1 expression induced an intensive zigzag shape of cell-cell junctions. These results suggest a role for ZO-1 in the regulation of cytoskeleton and shape of cell-cell junctions in MDCK cells and indicate the advantage of knockout analysis in cultured cells.
    Preview · Article · Aug 2014 · PLoS ONE
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    ABSTRACT: When the surface view of each epithelial cell is compared with a polygon, its sides correspond to cell-cell junctions, while its vertices correspond to tricellular contacts, whose roles in epithelial cell morphogenesis have not been well studied. Here, we show that tricellulin, which is localized at tricellular contacts, regulates F-actin organization via Cdc42. Tricellulin knockdown epithelial cells exhibit irregular polygonal shapes with curved cell borders and impaired organization of F-actin fibers around tricellular contacts during cell-cell junction formation. The N-terminal cytoplasmic domain of tricellulin binds to a Cdc42 guanine nucleotide exchange factor, Tuba, and activates Cdc42. A tricellulin mutant that lacks the ability of Tuba binding cannot rescue the curved cell border phenotype of tricellulin knockdown cells. These findings indicate that tricellular contacts play crucial roles in regulating the actomyosin-mediated apical junctional complex tension through the tricellulin-Tuba-Cdc42 system.
    Full-text · Article · Aug 2014 · Journal of Cell Science
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    ABSTRACT: Occludin is the first identified protein in the tight junction (TJ), but its function has remained for the most part obscure. TJs have been demonstrated to play important roles in the inner ear function, and occludin is expressed in all the epithelial TJs in the inner ear. Thus, we examined the inner ears of occludin-deficient (Occ(-/-)) mice. Although inner ears initially developed normally in Occ(-/-) mice, apoptosis occurs in hair cells in the organ of Corti around day 12 after birth, and deafness develops. Since hair cell degeneration was not observed in cochlear explant cultures of Occ(-/-) mice, environmental changes were considered to be the trigger of cell death. As for the vestibular system, both the morphologies and functions are normal in Occ(-/-) mice. These phenotypes of Occ(-/-) mice are very similar with those of claudin-14 or claudin-9 deficient mice, leading us to speculate on the existence of imbalance induced by TJ abnormalities, such as localized ionic components. Moreover, the occludin deficiency led to dislocalization of tricellulin, a gene responsible for human deafness DFNB49. The deafness in Occ(-/-) mice may be due to this dislocalization of tricellulin.
    Preview · Article · Jul 2014 · Biology Open
  • Mikio Furuse
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    ABSTRACT: Within an epithelial cellular sheet, the paracellular pathway can be divided into two routes: one between two adjacent cells and one at tricellular contacts, where the vertices of three cells meet. For epithelial barrier function, tight junctions restrict solute permeability through the paracellular pathway between two cells, while tricellular contacts contain specialized structures of tight junctions, named tricellular tight junctions (tTJs). Two types of membrane proteins, tricellulin and angulin family proteins (angulin-1/LSR, angulin-2/ILDR1 and angulin-3/ILDR2) have been identified as molecular components of tTJs. Angulins recruit triellulin to tTJs and these tTJ-associated proteins are required for normal tTJ formation as well as strong epithelial barrier function. Furthermore, mutations in tricellulin and angulin-2/ILDR1 genes cause autosomal recessive familial deafness, DFNB49 and DFNB42, respectively. Further analyses of the angulin-tricellulin system should lead to better understanding of the molecular mechanism and regulation of tTJs.
    No preview · Article · May 2014 · YAKUGAKU ZASSHI
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    ABSTRACT: Tricellular tight junctions (tTJs) are specialized structural variants of tight junctions within tricellular contacts of an epithelial sheet and comprise several transmembrane proteins including lipolysis-stimulated lipoprotein receptor (angulin-1/LSR) and tricellulin. To elucidate the mechanism of its formation, we carried out stepwise screening of kinase inhibitors followed by RNAi screening to identify kinases that regulate intracellular localization of angulin-1/LSR to the tTJs using a fluorescence image-based screen. We found that the activity of JNK1 and JNK2, but not JNK3, was required for the exclusive localization of angulin-1/LSR at the tTJs. Based on a bioinformatics approach, we estimated the potential phosphorylation site of angulin-1/LSR by JNK1 to be serine 288 and experimentally confirmed that JNK1 directly phosphorylates angulin-1/LSR at this site. We found that JNK2 was also involved in the phosphorylation of angulin-1/LSR. Furthermore, GFP-tagged angulin-1/LSR(S288A), in which serine 288 was substituted by alanine, was observed to be dispersed to bicellular junctions, indicating that phosphorylation of Ser288 is crucial for the exclusive localization of angulin-1/LSR and tricellulin at tTJs. Our fluorescence image-based screening for kinases inhibitor or siRNAs combined with the phosphorylation site prediction could become a versatile and useful tool to elucidate the mechanisms underlying the maintenance of tTJs regulated by kinase networks.
    No preview · Article · May 2014 · Genes to Cells
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    ABSTRACT: When the apicolateral border of epithelial cells is compared with a polygon, its sides correspond to the apical junctional complex, where cell adhesion molecules assemble from the plasma membranes of two adjacent cells. On the other hand, its vertices correspond to tricellular contacts, where the corners of three cells meet. Vertebrate tricellular contacts have specialized structures of tight junctions, termed tricellular tight junctions (tTJs). tTJs were identified by electron microscopic observations more than 40 years ago, but have been largely forgotten in epithelial cell biology since then. The identification of tricellulin and angulin family proteins as tTJ-associated membrane proteins has enabled us to study tTJs in terms of not only the paracellular barrier function but also unknown characteristics of epithelial cell corners via molecular biological approaches.
    Preview · Article · May 2014
  • Noriko Iwamoto · Tomohito Higashi · Mikio Furuse
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    ABSTRACT: The paracellular pathway of an epithelial cellular sheet can be divided into two parts: one between two adjacent cells sealed by tight junctions (TJs) and one at tricellular contacts (TCs), where the corners of three cells meet. At TCs of epithelial cells, there is a specialized mode of TJs, namely tricellular TJs (tTJs), required for full barrier function of the cellular sheet. However, tTJs have not been described in endothelial cells to date. Here, we investigated whether tTJs occur in endothelial cells by analyzing the TC localizations of tTJ markers, tricellulin and angulin family proteins (angulin-1/LSR, angulin-2/ILDR1, and angulin-3/ILDR2), by immunofluorescence staining of frozen sections of various tissues from adult mice. Endothelial TCs in most tissues revealed no detectable staining of tricellulin or angulins. However, tricellulin and angulin-1/LSR were specifically concentrated in TCs of brain and retinal endothelial cells, which form the blood-brain barrier (BBB) and inner blood-retinal barrier (BRB), respectively. Even in the brain, endothelial cells in the choroid plexus and the median eminence, one of the circumventricular organs, did not show concentration of tricellulin or angulins at TCs. These findings indicate the existence of tTJs in endothelial cells in vivo and suggest that tTJs impart important characteristics to the BBB and inner BRB.
    No preview · Article · Nov 2013 · Cell Structure and Function
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    ABSTRACT: Tricellulin is a tricellular tight junction-associated membrane protein that controls movement of solutes at these specialized cell intersections. Mutations in the gene encoding tricellulin, TRIC, lead to nonsyndromic deafness. In this issue of the JCI, Nayak et al. created a gene-targeted knockin mouse in order to mimic the pathology of a human TRIC mutation. Deafness appears to be caused either by an increase in the K+ ion concentration around the basolateral surfaces of the outer hair cells or, alternatively, by an increase in small molecules such as ATP around the hair bundle, leading to cellular dysfunction and degeneration. Furthermore, the mice have features suggestive of syndromic hearing loss, which may have implications for care and treatment of patients harboring TRIC mutations.
    Preview · Article · Aug 2013 · The Journal of clinical investigation
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    ABSTRACT: Tricellular tight junctions (tTJs) seal the extracellular space at tricellular contacts (TCs), where the corners of three epithelial cells meet. To date, the transmembrane proteins tricellulin and lipolysis-stimulated lipoprotein receptor (LSR) are known to be molecular components of tTJs. LSR recruits tricellulin to tTJs, and both proteins are required for the full barrier function of epithelial cellular sheets. In the present study, we show that two LSR-related proteins, immunoglobulin-like domain-containing receptor (ILDR) 1 and ILDR2, are also localized at TCs and recruit tricellulin. At least one of LSR, ILDR1 and ILDR2 was expressed in most of the epithelial tissues in mice. The expressions of LSR, ILDR1 and ILDR2 were generally complementary to each other, although LSR and ILDR1 were co-expressed in some epithelia. ILDR1 was required for the establishment of a strong barrier of the epithelium, similar to LSR, when introduced into cultured epithelial cells, whereas ILDR2 provided a much weaker barrier. We further analyzed human ILDR1, mutations in which cause a familial deafness, DFNB42, and found that most DFNB42-associated ILDR1 mutant proteins were defective in recruitment of tricellulin. We also found that tricellulin mutant proteins associated with another familial deafness, DFNB49, were not recruited to TCs by ILDR1. These findings show the heterogeneity of the molecular organization of tTJs in terms of the content of LSR, ILDR1 or ILDR2, and suggest that ILDR1-mediated recruitment of tricellulin to TCs is required for hearing. Given their common localization at epithelial cell corners and recruitment of tricellulin, we propose to designate LSR, ILDR1 and ILDR2 as angulin family proteins.
    Preview · Article · Aug 2013 · Journal of Cell Science
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    ABSTRACT: Tight junctions (TJs) form a selective barrier for ions, water, and macromolecules in simple epithelia. In keratinocytes and epidermis, TJs were shown to be involved in individual barrier functions. The absence of the TJ protein claudin-1 (Cldn1) in mice results in a skin-barrier defect characterized by lethal water loss. However, detailed molecular analyses of the various TJ barriers in keratinocytes and the contribution of distinct TJ proteins are missing. Herein, we discriminate TJ-dependent paracellular resistance from transcellular resistance in cultured keratinocytes using the two-path impedance spectroscopy. We demonstrate that keratinocyte TJs form a barrier for Na(+), Cl(-), and Ca(2+), and contribute to barrier function for water and larger molecules of different size. In addition, knockdown of Cldn1, Cldn4, occludin, and zonula occludens-1 increased paracellular permeabilities for ions and larger molecules, demonstrating that all of these TJ proteins contribute to barrier formation. Remarkably, Cldn1 and Cldn4 are not critical for TJ barrier function for water in submerged keratinocyte cultures. However, Cldn1 influences stratum corneum (SC) proteins important for SC water barrier function, and is crucial for TJ barrier formation for allergen-sized macromolecules.Journal of Investigative Dermatology advance online publication, 14 February 2013; doi:10.1038/jid.2012.507.
    No preview · Article · Feb 2013 · Journal of Investigative Dermatology
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    ABSTRACT: BACKGROUND: Tight junctions (TJs) contribute to the epithelial barrier function by preventing leakage of solutes through the intercellular space. In the skin, TJs occur in the stratum granulosum (SG), where claudin-1 and claudin-4 are expressed as adhesion molecules of TJs. Claudin-1-deficient (Cldn1(-/-)) mice die within one day of birth accompanied by excessive transepidermal water loss, indicating a critical role of TJs in the epidermal barrier function. However, it has been debated whether the impaired TJ function in the SG also affects the stratum corneum (SC) barrier function or whether it results in skin barrier defects despite a normal SC barrier. OBJECTIVE: To clarify whether the impaired TJ function affects the SC barrier function in Cldn1(-/-) mice. METHODS: The morphology, barrier function and biochemical characteristic of the SC were compared between Cldn1(-/-) and Cldn1(+/+) mice. RESULTS: Scanning electron microscopy demonstrated abnormally wrinkled and rough corneocytes in Cldn1(-/-) mice. Notably, the X-gal tracer easily permeated into the Cldn1(-/-) SC, and water evaporation through isolated Cldn1(-/-) SC sheets was significantly higher than that through Cldn1(+/+) SC sheets. Furthermore, the ceramide composition of the SC lipids and filaggrin processing were altered in Cldn1(-/-) mice. CONCLUSION: Cldn1(-/-) mice exhibited the abnormal SC formation and SC barrier defects. These findings demonstrate for the first time that TJs in the SG play crucial roles in the complete SC formation and SC barrier function.
    No preview · Article · Jan 2013 · Journal of dermatological science
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    ABSTRACT: Background Claudins have been demonstrated to be associated with inflammatory bowel disease (IBD), but the specific role of claudin-2 in colorectal inflammation remains undefined. Aims We aimed to determine the role of claudin-2 in TNFα-induced colorectal inflammation. Methods We used claudin-2 (−/−) mice to assess the role of claudin-2 in colon. The mice were intraperitoneally injected with 3 μg of recombinant murine TNFα, and the NF-κB signaling and mRNA expression levels of proinflammatory cytokines and myosin light chain kinase (MLCK) were evaluated. Moreover, in claudin-2 (−/−) mice, colitis was induced by the administration of dextran sodium sulfate (DSS). The involvement of claudin-2 in colorectal inflammation was also investigated using the Caco-2 human colon adenocarcinoma cell line, and the expression of claudin-2 was downregulated using claudin-2 siRNA. Results TNFα-induced colorectal inflammation via NF-κB signaling activation was enhanced in claudin-2 (−/−) mice compared with that in claudin-2 (+/+) mice. MLCK expression level in the colon tissue of claudin-2 (−/−) mice treated with TNFα was enhanced in comparison to that of the claudin-2 (+/+) mice. DSS-induced colitis was more severe in the claudin-2 (−/−) mice than in the claudin-2 (+/−) mice. In in vitro experiments, the decreased expression of claudin-2 enhanced the expressions of IL-6, IL-1β and MLCK. Conclusions Our findings concerning the role of claudin-2 in epithelial inflammatory responses enrich our collective understanding of mucosal homeostasis and intestinal diseases such as IBD. Furthermore, the results of this study indicate that claudin-2 and MLCK are potential therapeutic targets for treatments against intestinal disease.
    No preview · Article · Jan 2013 · Digestive Diseases and Sciences
  • Noriko Iwamoto · Mikio Furuse
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    ABSTRACT: Epithelial tissues divide external environment and internal milieu to maintain homeostasis. Tight junctions (TJ) are one mode of cell to cell contacts apparatus in epithelia, which control paracellular permeability of epithelial cellular sheets. The major components of TJ are claudins, that have tour transmembrane proteins and consist of multi-gene family. The blood- brain barrier (BBB) has a crucial role for maintaining homeostasis of CNS. TJs that exist in endothelial cells in brain microcapillary characterize barrier function of the BBB. To date, it is suggested that dysfunction of the BBB is involved in many neurogenic disorders. In developing drug delivery strategies, BBB- forming endothelial cells are promising therapeutic targets.
    No preview · Article · Jan 2013 · Drug Delivery System

Publication Stats

21k Citations
773.61 Total Impact Points

Institutions

  • 2008-2015
    • Kobe University
      • • Department of Physiology and Cell Biology
      • • Division of Cell Biology
      • • Division of Cellular and Molecular Medicine
      Kōbe, Hyōgo, Japan
  • 1994-2015
    • The Graduate University for Advanced Studies
      • • Division of Cerebral Structure
      • • Department of Information Physiology
      Миура, Kanagawa, Japan
  • 1996-2008
    • Kyoto University
      • Department of Cell Biology
      Kioto, Kyōto, Japan
  • 2001
    • Freie Universität Berlin
      Berlín, Berlin, Germany
  • 1999
    • The Jikei University School of Medicine
      Edo, Tōkyō, Japan