Novel mutation in the<i>CLDN1</i>gene in a Turkish family with neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome

Kirchmeier, Peter; Sayar, Ersin; Hotz, Alrun; Haußer, Ingrid; İşlek, Ali; Yılmaz, Aygen; Artan, Reha; Fischer, Judith

doi:10.1111/bjd.12724

Cited by 40 publications

(38 citation statements)

References 9 publications

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“…NISCH syndrome represents an extremely rare autosomal-recessive ichthyosis syndrome caused by mutations in the CLDN1 gene leading to its abolished expression in liver and skin (KO phenotype). First being described in 2002, only 12 cases have been reported [151,[155][156][157][158][159][160][161]. The clinical manifestation is variable ranging from absent or regressive cholestasis to progressive liver disease with liver failure.…”

Section: Primary Perturbation Of Tight Junction Proteins In Biliary Dmentioning

confidence: 99%

Tight Junction Proteins and the Biology of Hepatobiliary Disease

Roehlen

Suarez

Saghire

et al. 2020

IJMS

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Tight junctions (TJ) are intercellular adhesion complexes on epithelial cells and composed of integral membrane proteins as well as cytosolic adaptor proteins. Tight junction proteins have been recognized to play a key role in health and disease. In the liver, TJ proteins have several functions: they contribute as gatekeepers for paracellular diffusion between adherent hepatocytes or cholangiocytes to shape the blood-biliary barrier (BBIB) and maintain tissue homeostasis. At non-junctional localizations, TJ proteins are involved in key regulatory cell functions such as differentiation, proliferation, and migration by recruiting signaling proteins in response to extracellular stimuli. Moreover, TJ proteins are hepatocyte entry factors for the hepatitis C virus (HCV)—a major cause of liver disease and cancer worldwide. Perturbation of TJ protein expression has been reported in chronic HCV infection, cholestatic liver diseases as well as hepatobiliary carcinoma. Here we review the physiological function of TJ proteins in the liver and their implications in hepatobiliary diseases.

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Section: Primary Perturbation Of Tight Junction Proteins In Biliary Dmentioning

confidence: 99%

Tight Junction Proteins and the Biology of Hepatobiliary Disease

Roehlen

Suarez

Saghire

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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“…The expression patterns of claudins vary according to cell type and contribute to a variety of paracellular barrier functions that specifically maintain the homeostasis of tissues and organs (4). In the skin, TJs are key contributors to the epidermal paracellular barrier, and claudin-1 (CLDN1), a main component of TJs in the epidermis, is reported to be indispensable for this barrier function; abnormalities in CLDN1 cause human skin diseases (5)(6)(7)(8)(9). However, because Cldn1 knock-out (KO) mice die within 1 d of birth due to dehydration (10,11), it has been difficult to study how Cldn1 contributes to skin diseases.…”

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confidence: 99%

Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis

Tokumasu

Yamaga

Yamazaki

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

112

116

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Atopic dermatitis (AD) is a chronic inflammatory skin disease in humans. It was recently noted that the characteristics of epidermal barrier functions critically influence the pathological features of AD. Evidence suggests that claudin-1 (CLDN1), a major component of tight junctions (TJs) in the epidermis, plays a key role in human AD, but the mechanism underlying this role is poorly understood. One of the main challenges in studying CLDN1's effects is that Cldn1 knock-out mice cannot survive beyond 1 d after birth, due to lethal dehydration. Here, we established a series of mouse lines that express Cldn1 at various levels and used these mice to study Cldn1's effects in vivo. Notably, we discovered a dose-dependent effect of Cldn1's expression in orchestrating features of AD. In our experimental model, epithelial barrier functions and morphological changes in the skin varied exponentially with the decrease in Cldn1 expression level. At low Cldn1 expression levels, mice exhibited morphological features of AD and an innate immune response that included neutrophil and macrophage recruitment to the skin. These phenotypes were especially apparent in the infant stages and lessened as the mice became adults, depending on the expression level of Cldn1. Still, these adult mice with improved phenotypes showed an enhanced hapten-induced contact hypersensitivity response compared with WT mice. Furthermore, we revealed a relationship between macrophage recruitment and CLDN1 levels in human AD patients. Our findings collectively suggest that CLDN1 regulates the pathogenesis, severity, and natural course of human AD.claudin-1 | tight junctions | atopic dermatitis

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Novel mutation in theCLDN1gene in a Turkish family with neonatal ichthyosis sclerosing cholangitis (NISCH) syndrome

Cited by 40 publications

References 9 publications

Tight Junction Proteins and the Biology of Hepatobiliary Disease

Tight Junction Proteins and the Biology of Hepatobiliary Disease

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

Dose-dependent role of claudin-1 in vivo in orchestrating features of atopic dermatitis

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