21 results match your criteria filaggrin monomers

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Hydrochannel-Containing Hydrophobic Polymers by Inverse Emulsion Polymerization for Moisture-Driven Actuators.

ACS Appl Mater Interfaces 2020 Dec 23;12(49):55223-55230. Epub 2020 Nov 23.

Materials Science and Engineering Program, University of California, San Diego, 9500 Gilman Dr., La Jolla, California 92093, United States.

Two physical properties in polymers, hydrophobic and water-absorptive, are known to be incompatible. However, human skin in nature has a hydrophobic surface and yet absorbs water throughout hydrophilic amino acid sequences in filaggrin, one of the abundant proteins in our outermost skin layer. Although present in nature, a hydrophilic path network in a hydrophobic polymer is difficult to synthesize because of poor wettability and immiscibility between the two types of materials. Read More

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December 2020

Bleomycin hydrolase regulates the release of chemokines important for inflammation and wound healing by keratinocytes.

Sci Rep 2019 12 31;9(1):20407. Epub 2019 Dec 31.

Bioscience COPD/IPF, Research and Early Development, Respiratory, Inflammation and Autoimmune (RIA), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Bleomycin hydrolase (BLMH) is a well-conserved cysteine protease widely expressed in several mammalian tissues. In skin, which contains high levels of BLMH, this protease is involved in the degradation of citrullinated filaggrin monomers into free amino acids important for skin hydration. Interestingly, the expression and activity of BLMH is reduced in patients with atopic dermatitis (AD) and psoriasis, and BLMH knockout mice acquire tail dermatitis. Read More

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December 2019

Filaggrin Expression and Processing Deficiencies Impair Corneocyte Surface Texture and Stiffness in Mice.

J Invest Dermatol 2020 03 31;140(3):615-623.e5. Epub 2019 Aug 31.

Amsterdam UMC, University of Amsterdam, Coronel Institute of Occupational Health, Amsterdam Public Health research institute, Amsterdam, Netherlands. Electronic address:

Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp), filaggrin (Flg and Flg), filaggrin-hornerin (FlgHrnr), and bleomycin hydrolase (Blmh) were investigated. Read More

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LPA Induces Keratinocyte Differentiation and Promotes Skin Barrier Function through the LPAR1/LPAR5-RHO-ROCK-SRF Axis.

J Invest Dermatol 2019 05 14;139(5):1010-1022. Epub 2018 Nov 14.

Center for Innovation in Immunoregulation Technology and Therapeutics, Kyoto University Graduate School of Medicine, Kyoto, Japan; Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address:

The skin barrier protects the body from water loss, allergens, and pathogens. Profilaggrin is produced by differentiated keratinocytes and is processed into filaggrin monomers. These monomers cross-link keratin filaments and are also decomposed to natural moisturizing factors in the stratum corneum for skin hydration and barrier function. Read More

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Refined Immunochemical Characterization in Healthy Dog Skin of the Epidermal Cornification Proteins, Filaggrin, and Corneodesmosin.

J Histochem Cytochem 2019 02 10;67(2):85-97. Epub 2018 Sep 10.

UDEAR, INSERM, University of Toulouse, Toulouse, France.

Filaggrin (FLG) and corneodesmosin (CDSN) are two key proteins of the human epidermis. FLG loss-of-function mutations are the strongest genetic risk factors for human atopic dermatitis. Studies of the epidermal distribution of canine FLG and CDSN are limited. Read More

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February 2019

Concentration of filaggrin monomers, its metabolites and corneocyte surface texture in individuals with a history of atopic dermatitis and controls.

J Eur Acad Dermatol Venereol 2018 May 12;32(5):796-804. Epub 2018 Feb 12.

Department of Dermatology and Allergy, National Allergy Research Centre, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.

Background: Atopic dermatitis (AD) is characterized by skin barrier dysfunction. Notably, a high number of nano-scale protrusions on the surface of corneocytes, which can be expressed by the Dermal Texture Index (DTI), were recently associated with paediatric AD, loss-of-function mutations in filaggrin gene (FLG) and reduced levels of natural moisturizing factors (NMF). No study has so far examined the association between these parameters and monomeric filaggrin levels in adults. Read More

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A de novo variant in the ASPRV1 gene in a dog with ichthyosis.

PLoS Genet 2017 Mar 1;13(3):e1006651. Epub 2017 Mar 1.

Institute of Genetics, Vetsuisse Faculty, University of Bern, Bern, Switzerland.

Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. Read More

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Pelota Regulates Epidermal Differentiation by Modulating BMP and PI3K/AKT Signaling Pathways.

J Invest Dermatol 2016 08 7;136(8):1664-1671. Epub 2016 May 7.

Institute of Human Genetics, University of Göttingen, D-37073 Göttingen, Germany. Electronic address:

The depletion of evolutionarily conserved pelota protein causes impaired differentiation of embryonic and spermatogonial stem cells. In this study, we show that temporal deletion of pelota protein before epidermal barrier acquisition leads to neonatal lethality due to perturbations in permeability barrier formation. Further analysis indicated that this phenotype is a result of failed processing of profilaggrin into filaggrin monomers, which promotes the formation of a protective epidermal layer. Read More

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Pyrrolidone carboxylic acid levels or caspase-14 expression in the corneocytes of lesional skin correlates with clinical severity, skin barrier function and lesional inflammation in atopic dermatitis.

J Dermatol Sci 2014 Dec 30;76(3):231-9. Epub 2014 Sep 30.

Department of Dermatology, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 220-701 Korea. Electronic address:

Background: Dry skin in atopic dermatitis (AD) mainly results from barrier impairment due to deficiency of ceramide and natural moisturizing factors including pyrrolidone carboxylic acid (PCA) in stratum corneum (SC). Caspase-14 cleaves filaggrin monomers to free amino acids and their derivatives such as PCA, contributing natural moisturizing factors. Cytokines in the corneocytes represent cutaneous inflammation severity of AD patients. Read More

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December 2014

Mice deficient for the epidermal dermokine β and γ isoforms display transient cornification defects.

J Cell Sci 2014 Jul 2;127(Pt 13):2862-72. Epub 2014 May 2.

UMR 5165 / U1056 'Différenciation Epidermique et Autoimmunité Rhumatoïde' (CNRS - INSERM - Université Toulouse III - CHU de Toulouse), Hôpital Purpan, Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France

Expression of the human dermokine gene (DMKN) leads to the production of four dermokine isoform families. The secreted α, β and γ isoforms have an epidermis-restricted expression pattern, with Dmkn β and γ being specifically expressed by the granular keratinocytes. The δ isoforms are intracellular and ubiquitous. Read More

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Recombinant filaggrin is internalized and processed to correct filaggrin deficiency.

J Invest Dermatol 2014 Feb 21;134(2):423-429. Epub 2013 Jun 21.

Casey Eye Institute, Oregon Health and Sciences University, Portland, Oregon, USA.

This study was designed to engineer a functional filaggrin (FLG) monomer linked to a cell-penetrating peptide (RMR) and to test the ability of this peptide to penetrate epidermal tissue as a therapeutic strategy for genetically determined atopic dermatitis (AD). A single repeat of the murine filaggrin gene (Flg) was covalently linked to a RMR motif and cloned into a bacterial expression system for protein production. Purified FLG+RMR (mFLG+RMR) was applied in vitro to HEK-293T cells and a reconstructed human epidermis (RHE) tissue model. Read More

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February 2014

Epidermal structure created by canine hair follicle keratinocytes enriched with bulge cells in a three-dimensional skin equivalent model in vitro: implications for regenerative therapy of canine epidermis.

Vet Dermatol 2013 Feb;24(1):77-83.e19-20

Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.

Background: Keratinocytes in the hair follicle bulge region have a high proliferative capacity, with characteristics of epithelial stem cells. This cell population might thus be an ideal source for generating the interfollicular epidermis in a canine skin equivalent.

Hypothesis/objectives: This study was designed to determine the ability of canine hair follicle bulge cell-enriched keratinocytes to construct canine living skin equivalents with interfollicular epidermis in vitro. Read More

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February 2013

The stratum corneum: the rampart of the mammalian body.

Vet Dermatol 2013 Feb;24(1):60-72.e15-6

Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Tokyo, Japan.

Background: The stratum corneum (SC) is the outermost region of the epidermis and plays key roles in cutaneous barrier function in mammals. The SC is composed of 'bricks', represented by flattened, protein-enriched corneocytes, and 'mortar', represented by intercellular lipid-enriched layers. As a result of this 'bricks and mortar' structure, the SC can be considered as a 'rampart' that encloses water and solutes essential for physiological homeostasis and that protects mammals from physical, chemical and biological assaults. Read More

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February 2013

Characterization of canine filaggrin: gene structure and protein expression in dog skin.

Vet Dermatol 2013 Feb;24(1):25-31.e7

Laboratory of Veterinary Internal Medicine, Tokyo University of Agriculture and Technology, Tokyo, Japan.

Background: Filaggrin (FLG) is a key protein for skin barrier formation and hydration of the stratum corneum. In humans, a strong association between FLG gene mutations and atopic dermatitis has been reported. Although similar pathogenesis and clinical manifestation have been argued in canine atopic dermatitis, our understanding of canine FLG is limited. Read More

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February 2013

Regulatory role for the profilaggrin N-terminal domain in epidermal homeostasis.

J Invest Dermatol 2012 Oct 24;132(10):2376-2385. Epub 2012 May 24.

Biosciences, Unilever R&D, Trumbull, Connecticut, USA.

It is well known that profilaggrin, after its release from keratohyalin granules through dephosphorylation, becomes enzymatically processed into individual filaggrin monomers. The roles for filaggrin monomers in aggregating keratin filaments, as a component of the cornified cell envelope, and as a source of natural moisturizing factor are well established. A specific N-terminal fragment, called the PF-AB domain, becomes proteolytically released as well, but much less is known about its functional role in epidermal development. Read More

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October 2012

Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose-dependent effect.

J Invest Dermatol 2012 Jan 10;132(1):98-104. Epub 2011 Nov 10.

Dermatology and Genetic Medicine, Division of Molecular Medicine, University of Dundee, Dundee, UK.

Loss-of-function variants within the filaggrin gene (FLG) increase the risk of atopic dermatitis. FLG also demonstrates intragenic copy number variation (CNV), with alleles encoding 10, 11, or 12 filaggrin monomers; hence, CNV may affect the amount of filaggrin expressed in the epidermis. A total of 876 Irish pediatric atopic dermatitis cases were compared with 928 population controls to test the hypothesis that CNV within FLG affects the risk of atopic dermatitis independently of FLG-null mutations. Read More

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January 2012

Regulation of caspase 14 expression in keratinocytes by inflammatory cytokines--a possible link between reduced skin barrier function and inflammation?

Exp Dermatol 2011 Aug 4;20(8):633-6. Epub 2011 May 4.

Department of Dermato-venereology, Aarhus University Hospital, Aarhus C, Denmark.

Caspase 14 is a unique member of the cysteinyl aspartate-specific proteinase family. Its expression is confined primarily to cornified epithelium such as the skin. Caspase 14 has been associated with the processing of filaggrin monomers and the development of natural moisturising factors of the skin, and thus, it could be speculated that caspase 14 dysregulation is implicated in the development of an impaired skin barrier function. Read More

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Ichthyosis, follicular atrophoderma, and hypotrichosis caused by mutations in ST14 is associated with impaired profilaggrin processing.

J Invest Dermatol 2009 Apr 9;129(4):862-9. Epub 2008 Oct 9.

Division of Dermatogenetics, Cologne Center for Genomics, University of Cologne, Cologne, Germany.

Congenital ichthyosis encompasses a heterogeneous group of disorders of cornification. Isolated forms and syndromic ichthyosis can be differentiated. We have analyzed two consanguineous families from the United Arab Emirates and Turkey with an autosomal recessive syndrome of diffuse congenital ichthyosis, patchy follicular atrophoderma, generalized and diffuse nonscarring hypotrichosis, marked hypohidrosis, and woolly hair (OMIM 602400). Read More

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Defect of hepatocyte growth factor activator inhibitor type 1/serine protease inhibitor, Kunitz type 1 (Hai-1/Spint1) leads to ichthyosis-like condition and abnormal hair development in mice.

Am J Pathol 2008 Nov 2;173(5):1464-75. Epub 2008 Oct 2.

Department of Pathology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan.

Hepatocyte growth factor activator inhibitor type 1 (HAI-1)/serine protease inhibitor, Kunitz type 1 (SPINT1) is a membrane-bound, serine proteinase inhibitor initially identified as an inhibitor of hepatocyte growth factor activator. It also inhibits matriptase and prostasin, both of which are membrane-bound serine proteinases that have critical roles in epidermal differentiation and function. In this study, skin and hair phenotypes of mice lacking the Hai-1/Spint1 gene were characterized. Read More

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November 2008

Lethal, neonatal ichthyosis with increased proteolytic processing of filaggrin in a mouse model of Netherton syndrome.

Hum Mol Genet 2005 Jan 8;14(2):335-46. Epub 2004 Dec 8.

MRC Laboratory of Molecular Biology, Cambridge, UK.

Netherton syndrome is an autosomal recessive multisystemic disorder characterized by congenital ichthyosiform erythroderma, hair shaft defects and atopy, caused by mutations within the human SPINK5 gene. To investigate the development of this disease, we have cloned mouse spink5 and created mice with a mutated premature stop codon at amino acid R820X, to produce an allele that closely mimics a point mutation (E827X) in human SPINK5. Newborn spink5(R820X/R820X) mice develop a lethal, severe ichthyosis with a loss of skin barrier function and dehydration, resulting in death within a few hours of birth, similar to that observed in patients with severe Netherton syndrome. Read More

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January 2005

Cytoplasmic processing of human profilaggrin by active mu-calpain.

Biochem Biophys Res Commun 1997 Jun;235(3):652-6

Department of Dermatology, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.

The differentiation of keratinocytes involves numerous steps including the formation of the cornified envelope and the aggregation of keratin filaments by filaggrin monomer molecules. In this study, we investigated whether mu-calpain is involved in the processing of profilaggrin to filaggrin monomers by using both an active mu-calpain specific antibody and a 27-mer synthetic calpastatin peptide, a cell-permeable calpain-specific inhibitor. Upon incubation of cultured keratinocytes with Ca2+ for 96 hours, active mu-calpain with a molecular mass of 76 kDa appeared preceded by an increase in mu-calpain mRNA. Read More

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