Knockdown of Filaggrin in a Three-Dimensional Reconstructed Human Epidermis Impairs Keratinocyte Differentiation Valérie Pendaries, Jeremy Malaisse,

Slides:

Advertisements

Similar presentations

Nan-Hyung Kim, Ai-Young Lee Journal of Investigative Dermatology

Advertisements

Hanna Niehues, MSc, Joost Schalkwijk, PhD, Ivonne M. J. J

The δ-Opioid Receptor Affects Epidermal Homeostasis via ERK-Dependent Inhibition of Transcription Factor POU2F3 Christine Neumann, Mei Bigliardi-Qi,

Loss of sirtuin 1 (SIRT1) disrupts skin barrier integrity and sensitizes mice to epicutaneous allergen challenge Mei Ming, PhD, Baozhong Zhao, PhD, Christopher.

Persistence of Both Peripheral and Non-Peripheral Corneodesmosomes in the Upper Stratum Corneum of Winter Xerosis Skin Versus only Peripheral in Normal.

Keratin 9 Is Required for the Structural Integrity and Terminal Differentiation of the Palmoplantar Epidermis Dun Jack Fu, Calum Thomson, Declan P. Lunny,

Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation Susanne Grond, Franz P.W. Radner, Thomas.

The Desmosomal Protein Desmoglein 1 Aids Recovery of Epidermal Differentiation after Acute UV Light Exposure Jodi L. Johnson, Jennifer L. Koetsier, Anna.

Rab11a Is Essential for Lamellar Body Biogenesis in the Human Epidermis Marie Reynier, Sophie Allart, Elise Gaspard, Alain Moga, Dominique Goudounèche,

Transglutaminase 3 Protects against Photodamage

Loss of Keratin K2 Expression Causes Aberrant Aggregation of K10, Hyperkeratosis, and Inflammation Heinz Fischer, Lutz Langbein, Julia Reichelt, Silke.

CD44 Regulates Tight-Junction Assembly and Barrier Function

Integrin-Linked Kinase Is Indispensable for Keratinocyte Differentiation and Epidermal Barrier Function Samar Sayedyahossein, Alena Rudkouskaya, Valerie.

Hyaluronidase-1 Is Mainly Functional in the Upper Granular Layer, Close to the Epidermal Barrier Jérémy Malaisse, Céline Evrard, Damien Feret, Vanessa.

UVB-Induced Skin Inflammation and Cutaneous Tissue Injury Is Dependent on the MHC Class I–Like Protein, CD1d Stephan Ryser, Marlène Schuppli, Beatrice.

Verena N. Lorenz, Michael P. Schön, Cornelia S. Seitz

Topical ROR Inverse Agonists Suppress Inflammation in Mouse Models of Atopic Dermatitis and Acute Irritant Dermatitis Jun Dai, Min-Kyung Choo, Jin Mo.

Sirpa Aho, Clive R. Harding, Jian-Ming Lee, Helen Meldrum, Carol A

Impaired Wound Repair in Adult Endoglin Heterozygous Mice Associated with Lower NO Bioavailability Eduardo Pérez-Gómez, Mirjana Jerkic, Marta Prieto,

Malignant T Cells Secrete Galectins and Induce Epidermal Hyperproliferation and Disorganized Stratification in a Skin Model of Cutaneous T-Cell Lymphoma

Alteration of the EphA2/Ephrin-A Signaling Axis in Psoriatic Epidermis

Epidermal Lamellar Granules Transport Different Cargoes as Distinct Aggregates Akemi Ishida-Yamamoto, Michel Simon, Mari Kishibe, Yuki Miyauchi, Hidetoshi.

Peptidylarginine Deiminase Isoforms 1–3 Are Expressed in the Epidermis and Involved in the Deimination of K1 and Filaggrin Rachida Nachat, Marie-Claire.

Katja Schulze, Arnaud Galichet, Beyza S

IL-25 Enhances HSV-1 Replication by Inhibiting Filaggrin Expression, and Acts Synergistically with Th2 Cytokines to Enhance HSV-1 Replication Byung Eui.

Transglutaminase 3 Protects against Photodamage

Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation Susanne Grond, Franz P.W. Radner, Thomas.

Hyaluronan Metabolism in Human Keratinocytes and Atopic Dermatitis Skin Is Driven by a Balance of Hyaluronan Synthases 1 and 3 Jérémy Malaisse, Virginie.

Degradation of Corneodesmosome Proteins by Two Serine Proteases of the Kallikrein Family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7 Cécile Caubet, Nathalie Jonca,

Th2 Cytokines Increase Staphylococcus aureus Alpha Toxin–Induced Keratinocyte Death through the Signal Transducer and Activator of Transcription 6 (STAT6)

EGF Upregulates, Whereas TGF-β Downregulates, the Hyaluronan Synthases Has2 and Has3 in Organotypic Keratinocyte Cultures: Correlations with Epidermal.

Christina A. Young, Richard L

Matriptase Regulates Proliferation and Early, but Not Terminal, Differentiation of Human Keratinocytes Ya-Wen Chen, Jehng-Kang Wang, Fen-Pai Chou, Bai-Yao.

Thomas E. Stout, Trevor McFarland, John C

Marie-Thérèse Leccia Journal of Investigative Dermatology

Impaired Skin Regeneration and Remodeling after Cutaneous Injury and Chemically Induced Hyperplasia in Taps-Transgenic Mice Maike Hildenbrand, Verena.

Differential Expression of Matrix Metalloproteinases During Impaired Wound Healing of the Diabetes Mouse Steven J. Wall, Dr, Damon Bevan, David W. Thomas,

Influence of Th2 Cytokines on the Cornified Envelope, Tight Junction Proteins, and β- Defensins in Filaggrin-Deficient Skin Equivalents Stefan Hönzke,

Knockdown of Filaggrin in a Three-Dimensional Reconstructed Human Epidermis Impairs Keratinocyte Differentiation Valérie Pendaries, Jeremy Malaisse,

Abnormally Differentiating Keratinocytes in the Epidermis of Systemic Sclerosis Patients Show Enhanced Secretion of CCN2 and S100A9 Joanna Nikitorowicz-Buniak,

Abnormally Differentiating Keratinocytes in the Epidermis of Systemic Sclerosis Patients Show Enhanced Secretion of CCN2 and S100A9 Joanna Nikitorowicz-Buniak,

The Eumelanin Intermediate 5,6-Dihydroxyindole-2-Carboxylic Acid Is a Messenger in the Cross-Talk among Epidermal Cells Daniela Kovacs, Enrica Flori,

Mohammad Rashel, Ninche Alston, Soosan Ghazizadeh

Epidermal COX-2 Induction Following Ultraviolet Irradiation: Suggested Mechanism for the Role of COX-2 Inhibition in Photoprotection Catherine S. Tripp,

Epidermal RelA Specifically Restricts Contact Allergen–Induced Inflammation and Apoptosis in Skin Snehlata Kumari, Benjamin Herzberg, Ruth Pofahl, Thomas.

Establishment of Two Mouse Models for CEDNIK Syndrome Reveals the Pivotal Role of SNAP29 in Epidermal Differentiation Stina A. Schiller, Christina Seebode,

Stimulation of PPARα Promotes Epidermal Keratinocyte Differentiation In Vivo László G. Kömüves, Karen Hanley, Anne-Marie Lefebvre, Mao-Qiang Man, Dean.

Incomplete KLK7 Secretion and Upregulated LEKTI Expression Underlie Hyperkeratotic Stratum Corneum in Atopic Dermatitis Satomi Igawa, Mari Kishibe, Masako.

Ultraviolet B Irradiation Induces Expansion of Intraepithelial Tumor Cells in a Tissue Model of Early Cancer Progression Norbert E. Fusenig Journal.

K6PC-5, a Direct Activator of Sphingosine Kinase 1, Promotes Epidermal Differentiation Through Intracellular Ca2+ Signaling Jeong Hee Hong, Jong-Kyung.

Genetic and Pharmacological Analysis Identifies a Physiological Role for the AHR in Epidermal Differentiation Ellen H. van den Bogaard, Michael A. Podolsky,

Deimination of Human Hornerin Enhances its Processing by Calpain-1 and its Cross- Linking by Transglutaminases Chiung-Yueh Hsu, Géraldine Gasc, Anne-Aurélie.

Leah C. Biggs, Lindsey Rhea, Brian C. Schutte, Martine Dunnwald

Increased Sensitivity of Histidinemic Mice to UVB Radiation Suggests a Crucial Role of Endogenous Urocanic Acid in Photoprotection Caterina Barresi,

Yuko Oda, Lizhi Hu, Vadim Bul, Hashem Elalieh, Janardan K

Localization of Serine Racemase and Its Role in the Skin

Peptidylarginine Deiminase Isoforms Are Differentially Expressed in the Anagen Hair Follicles and Other Human Skin Appendages Rachida Nachat, Marie-Claire.

Denis Mehic, Latifa Bakiri, Minoo Ghannadan, Erwin F

Epidermal Inactivation of the Glucocorticoid Receptor Triggers Skin Barrier Defects and Cutaneous Inflammation Lisa M. Sevilla, Víctor Latorre, Ana Sanchis,

Knockdown of Filaggrin Impairs Diffusion Barrier Function and Increases UV Sensitivity in a Human Skin Model Michael Mildner, Jiang Jin, Leopold Eckhart,

Loss of Normal Profilaggrin and Filaggrin in Flaky Tail (ft/ft) Mice: an Animal Model for the Filaggrin-Deficient Skin Disease Ichthyosis Vulgaris Richard.

Development of an Ichthyosiform Phenotype in Alox12b-Deficient Mouse Skin Transplants Silvia de Juanes, Nikolas Epp, Susanne Latzko, Mareen Neumann,

Nan-Hyung Kim, Ai-Young Lee Journal of Investigative Dermatology

Keratinocyte Differentiation in Hyperproliferative Epidermis: Topical Application of PPARα Activators Restores Tissue Homeostasis László G. Kömüves,

Activation of TLR3 in Keratinocytes Increases Expression of Genes Involved in Formation of the Epidermis, Lipid Accumulation, and Epidermal Organelles

Kallikrein-Related Peptidase 8–Dependent Skin Wound Healing Is Associated with Upregulation of Kallikrein-Related Peptidase 6 and PAR2 Mari Kishibe,

Redistribution of LRIG Proteins in Psoriasis

Bleomycin hydrolase downregulation in lesional skin of adult atopic dermatitis patients is independent of FLG gene mutations Laurence Pellerin, PhD,

Keratinocyte Proline-Rich Protein Deficiency in Atopic Dermatitis Leads to Barrier Disruption Hiraku Suga, Tomonori Oka, Makoto Sugaya, Yasunari Sato,

Interaction of the Profilaggrin N-Terminal Domain with Loricrin in Human Cultured Keratinocytes and Epidermis Kozo Yoneda, Toshitaka Nakagawa, Owen T.

Presentation transcript:

Knockdown of Filaggrin in a Three-Dimensional Reconstructed Human Epidermis Impairs Keratinocyte Differentiation Valérie Pendaries, Jeremy Malaisse, Laurence Pellerin, Marina Le Lamer, Rachida Nachat, Sanja Kezic, Anne-Marie Schmitt, Carle Paul, Yves Poumay, Guy Serre, Michel Simon Journal of Investigative Dermatology Volume 134, Issue 12, Pages 2938-2946 (December 2014) DOI: 10.1038/jid.2014.259 Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Expression of filaggrin is highly reduced in RHE produced with shFLG keratinocytes. (a–c) Fully differentiated shc- and shFLG-reconstructed human epidermis (RHE) were analyzed by quantitative real-time reverse-transcriptase–PCR (a), and by both western blotting (b) and immunofluorescence (c; in red) performed with an AHF3 antibody. Immunodetected profilaggrin and filaggrin monomers were quantified and normalized to GAPDH levels. Error bars represent the SD calculated from three experiments performed with keratinocytes from three different donors, each in triplicate. The polycarbonate filter–epidermal junction is indicated by thin lines. Bars = 50 μm. Journal of Investigative Dermatology 2014 134, 2938-2946DOI: (10.1038/jid.2014.259) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Filaggrin deficiency leads to altered epidermal morphology. (a) Sections of paraffin-embedded shc- and shFLG-reconstructed human epidermis (RHE) were stained with hematoxylin and eosin. One representative experiment of three is shown. Bars = 20 μm. (b) Normal epidermis (NE), shc-, and shFLG-RHE were analyzed by electron microscopy, as described in Supplementary Materials and Methods online. Corneodesmosomes (white arrows), desmosomes (black arrows), and keratohyalin granules (arrowheads) were observed. The stratum corneum (SC) and granulosum (G) are indicated. Scale bars are shown. Journal of Investigative Dermatology 2014 134, 2938-2946DOI: (10.1038/jid.2014.259) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 The stratum corneum properties of filaggrin-deficient RHE are impaired. (a) A solution of Lucifer yellow was applied onto the stratum corneum of the shc- and shFLG-reconstructed human epidermis (RHE) . After 6 hours, penetration of the dye was investigated using sections of paraffin-embedded tissue observed under a fluorescence microscope. The stratum corneum surface (thick line) and the polycarbonate filter (thin lines) are indicated. Bars = 20 μm. (b) Urocanic acid (t-UCA) and pyrrolidone carboxylic acid (PCA) amounts were quantified using HPLC in lysates of shc-RHE (n=8) and shFLG-RHE (n=9). *P<0.05; **P<0.001. Means and SE are indicated. (c) Shc- and shFLG-RHE were irradiated with UV-B (150 mJ cm-2), and the active caspase-3 was detected using indirect immunofluorescence (in red). DNA was labeled with 4′,6′-diamidino-2-phenylindole (in blue). Journal of Investigative Dermatology 2014 134, 2938-2946DOI: (10.1038/jid.2014.259) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Filaggrin knockdown alters keratinocyte differentiation. (a–d) Expression of proteins in shc- and shFLG-reconstructed human epidermis (RHE) was either analyzed by western blotting (a) and quantified (b) or investigated by immunofluorescence staining (c) and quantitative real-time reverse-transcriptase–PCR (d). FLG, filaggrin; HRNR, hornerin; K, keratin; LOR, loricrin; DSG, desmoglein; DSC, desmocollin; CASP14, caspase-14 (both precursor (*) and active (**) forms); BLMH, bleomycin hydrolase; CDSN, corneodesmosin; CLDN, claudin; IVL, involucrin; CDH1, E-cadherin; CAPN, calpain; GAPDH, glyceraldehyde 3-phosphate dehydrogenase. Error bars represent the SD calculated as indicated in the legend of Figure 1. The polycarbonate filter– and dermo-epidermal junctions are indicated by dashed lines. Scale bars = 20 μm. **P<0.01; ***P<0.001. Journal of Investigative Dermatology 2014 134, 2938-2946DOI: (10.1038/jid.2014.259) Copyright © 2014 The Society for Investigative Dermatology, Inc Terms and Conditions