Time- and dose-dependent claudin contribution to biological functions: Lessons from claudin-1 in skin

Tokumasu, Reitaro; Tamura, Atsushi; Tsukita, Sachiko

doi:10.1080/21688370.2017.1336194

Cited by 15 publications

(13 citation statements)

References 31 publications

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“…When comparing the mouse skin epithelium to palate epithelium, we identified Cldn1 as the most over expressed TJ gene in skin, with Cldn8 being most over expressed in the palate. High Cldn1 expression observed in the tail epidermal cell population is consistent with previous reports on this TJ gene as being one of the major transmembrane proteins involved in forming the epidermal paracellular barrier in skin [29]. Interestingly, high Cldn8 expression has been observed in clinical cancer cell samples relative to benign controls and was shown to promote a pro-migratory and proliferative phenotype in multiple studies [30,31] which is in line with the more proliferative phenotype observed in oral epithelium.…”

Section: Discussionsupporting

confidence: 90%

Differential Expression and Function of Bicellular Tight Junctions in Skin and Oral Wound Healing

Leonardo

Shi

Chen

et al. 2020

IJMS

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Bicellular tight junctions are multiprotein complexes that are required for maintenance of barrier function and fence function in epithelial tissues. Wound healing in the oral cavity leads to minimal scar formation compared to the skin, and the precise mechanisms for this regenerative response remain to be elucidated. We hypothesized that oral and skin tissues express a different tight junction repertoire both at baseline and during the wound healing response, and that these molecules may be critical to the differential repair between the two tissues. We re-analyzed a mouse skin and palate epithelium microarray dataset to identify the tight junction repertoire of these tissue types. We then re-analyzed a skin and tongue wound healing microarray dataset to see how expression levels of tight junction genes change over time in response to injury. We performed in vitro scratch assays on human oral and skin keratinocyte cell lines to assay for tight junction expression over time, tight junction expression in response to lipopolysaccharide and histamine treatment, and the effects of siRNA knockdown of claudin 1 or occludin on migration and proliferation. Our data showed that oral and skin epithelium expressed different tight junction genes at baseline and during the wound healing response. Knockdown of claudin 1 or occludin led to changes in proliferation and migration in human skin keratinocytes but not oral keratinocytes. Furthermore, we also showed that skin keratinocytes were more permeable than oral keratinocytes upon histamine treatment. In conclusion, this study highlights a specific subset of functional tight junction genes that are differentially expressed between the oral and skin tissues, which may contribute to the mechanisms leading to distinct healing phenotypes in response to injury in the two tissues.

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Section: Discussionsupporting

confidence: 90%

Differential Expression and Function of Bicellular Tight Junctions in Skin and Oral Wound Healing

Leonardo

Shi

Chen

et al. 2020

IJMS

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“…3). Cldn-1 has previously been shown to be indispensable for the barrier function of mammalian skin, where mutations in this protein resulted in multiple skin defects and increased epidermal paracellular permeability (Hadj-Rabia et al, 2004;Brandner, 2009;Kirschner et al, 2009;De Benedetto et al, 2011;Günzel and Yu, 2013;Kirchmeier et al, 2014;Tokumasu et al, 2017). Cldn-1-deficient mice died shortly after birth as a result of evaporative water loss through the skin, implying that Cldn-1 may act as a water barrier in mammalian skin (Furuse et al, 2002).…”

Section: Effect Of Bd Infection On Cldn-1 Ocln and Tric Abundancementioning

confidence: 99%

A lethal fungal pathogen directly alters tight junction proteins in the skin of a susceptible amphibian

Gauberg

Cramp

et al. 2018

Journal of Experimental Biology

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Bacterial and viral pathogens can weaken epithelial barriers by targeting and disrupting tight junction (TJ) proteins. However, comparatively little is known about the direct effects of fungal pathogens on TJ proteins and their expression. The disease chytridiomycosis, caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd), is threatening amphibian populations worldwide. Bd is known to infect amphibian skin and disrupt cutaneous osmoregulation. However, exactly how this occurs is poorly understood. This study considered the impact of Bd infection on the barrier properties of the Australian green tree frog (Litoria caerulea) epidermis by examining how inoculation of animals with Bd influenced the paracellular movement of FITC-dextran (4 kDa, FD-4) across the skin in association with alterations in the mRNA and protein abundance of select TJ proteins of the epidermal TJ complex. It was observed that Bd infection increased paracellular movement of FD-4 across the skin linearly with fungal infection load. In addition, Bd infection increased transcript abundance of the tricellular TJ (tTJ) protein tricellulin (Tric) as well as the bicellular TJ (bTJ) proteins occludin (Ocln), claudin (Cldn)-1, Cldn-4 and the scaffolding TJ protein zonula occludens 1 (ZO-1). However, while Tric protein abundance increased in accord with changes in transcript abundance, protein abundance of Cldn-1 was significantly reduced and Ocln protein abundance was unchanged. Data indicate that disruption of cutaneous osmoregulation in L. caerulea following Bd infection occurs, at least in part, by an increase in epidermal paracellular permeability in association with compromised integrity of the epidermal TJ complex.

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“…Continuous Claudin-based TJs are present in the epidermis and these particular TJs are crucial for the barrier function of mammalian skin ( 17 ). In addition, Claudin-1 and -4 are involved in the pathogenesis of skin lesions ( 18 - 20 ). How Claudin-1 and -4 are regulated in response to ATRA is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

All‑trans retinoic acid alters the expression of the�tight�junction proteins Claudin‑1 and ‑4 and epidermal barrier function‑associated genes in the epidermis

Geng

2019

Int J Mol Med

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All-trans retinoic acid (ATRA) regulates skin cell proliferation and differentiation. ATRA is widely used in the treatment of skin diseases, but results in irritation, dryness and peeling, possibly due to an impaired skin barrier, although the exact mechanisms are unclear. The present study established an ATRA-associated dermatitis mouse model (n=32) in order to examine the molecular mechanisms of skin barrier impairment by ATRA. Changes in epidermal morphology and structure were observed using histological examination and transmission electron microscopy (TEM). Gene expression was analyzed by microarray chip assay. Histology and TEM demonstrated pronounced epidermal hyperproliferation and parakeratosis upon ATRA application. The stratum corneum layer displayed abnormal lipid droplets and cell-cell junctions, suggesting alterations in lipid metabolism and dysfunctional cell junctions. Gene expression profiling revealed that factors associated with epidermal barrier function were differentially expressed by ATRA, including those associated with tight junctions (TJs), cornified envelopes, lipids, proteases, protease inhibitors and transcription factors. In the mouse epidermis, Claudin-1 and -4 are proteins involved in TJs and have key roles in epidermal barrier function. ATRA reduced the expression and altered the localization of Claudin-1 in HaCaT immortalized keratinocytes and the mouse epidermis, which likely leads to the disruption of the epidermal barrier. By contrast, Claudin-4 was upregulated in HaCaT cells and the mouse epidermis following treatment with ATRA. In conclusion, ATRA exerts a dual effect on epidermal barrier genes: It downregulates the expression of Claudin-1 and upregulates the expression of Claudin-4. Claudin-4 upregulation may be a compensatory response for the disrupted barrier function caused by Claudin-1 downregulation.

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Time- and dose-dependent claudin contribution to biological functions: Lessons from claudin-1 in skin

Cited by 15 publications

References 31 publications

Differential Expression and Function of Bicellular Tight Junctions in Skin and Oral Wound Healing

Differential Expression and Function of Bicellular Tight Junctions in Skin and Oral Wound Healing

A lethal fungal pathogen directly alters tight junction proteins in the skin of a susceptible amphibian

All‑trans retinoic acid alters the expression of the�tight�junction proteins Claudin‑1 and ‑4 and epidermal barrier function‑associated genes in the epidermis

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