scholarly journals The Epidermis: Redox Governor of Health and Diseases

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 47
Author(s):  
Yosuke Ishitsuka ◽  
Dennis R. Roop
Keyword(s):  
Skin Diseases ◽  
Protective Layer ◽  
Xenobiotic Metabolism ◽  
Epidermal Differentiation ◽  
Erythroid Cell ◽  
Permeability Barrier ◽  
Related Factor ◽  
Stratum Granulosum ◽  
Epidermal Differentiation Complex ◽  
Uppermost Layer

A functional epithelial barrier necessitates protection against dehydration, and ichthyoses are caused by defects in maintaining the permeability barrier in the stratum corneum (SC), the uppermost protective layer composed of dead cells and secretory materials from the living layer stratum granulosum (SG). We have found that loricrin (LOR) is an essential effector of cornification that occurs in the uppermost layer of SG (SG1). LOR promotes the maturation of corneocytes and extracellular adhesion structure through organizing disulfide cross-linkages, albeit being dispensable for the SC permeability barrier. This review takes psoriasis and AD as the prototype of impaired cornification. Despite exhibiting immunological traits that oppose each other, both conditions share the epidermal differentiation complex as a susceptible locus. We also review recent mechanistic insights on skin diseases, focusing on the Kelch-like erythroid cell-derived protein with the cap “n” collar homology-associated protein 1/NFE2-related factor 2 signaling pathway, as they coordinate the epidermis-intrinsic xenobiotic metabolism. Finally, we refine the theoretical framework of thiol-mediated crosstalk between keratinocytes and leukocytes in the epidermis that was put forward earlier.

scholarly journals Effect of SUV39H1 Histone Methyltransferase Knockout on Expression of Differentiation-Associated Genes in HaCaT Keratinocytes

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2628
Author(s):  
Barbara Sobiak ◽  
Wiesława Leśniak
Keyword(s):  
Gene Expression ◽  
Skin Diseases ◽  
Human Keratinocytes ◽  
Histone Methyltransferase ◽  
Epidermal Differentiation ◽  
Gene Encoding ◽  
Epidermal Differentiation Complex ◽  
Expression Of Genes ◽  
State Dependent ◽  
Genomic Locations

Keratinocytes undergo a complex differentiation process, coupled with extensive changes in gene expression through which they acquire distinctive features indispensable for cells that form the external body barrier—epidermis. Disturbed epidermal differentiation gives rise to multiple skin diseases. The involvement of epigenetic factors, such as DNA methylation or histone modifications, in the regulation of epidermal gene expression and differentiation has not been fully recognized yet. In this work we performed a CRISPR/Cas9-mediated knockout of SUV39H1, a gene-encoding H3K9 histone methyltransferase, in HaCaT cells that originate from spontaneously immortalized human keratinocytes and examined changes in the expression of selected differentiation-specific genes located in the epidermal differentiation complex (EDC) and other genomic locations by RT-qPCR. The studied genes revealed a diverse differentiation state-dependent or -independent response to a lower level of H3K9 methylation. We also show, by means of chromatin immunoprecipitation, that the expression of genes in the LCE1 subcluster of EDC was regulated by the extent of trimethylation of lysine 9 in histone H3 bound to their promoters. Changes in gene expression were accompanied by changes in HaCaT cell morphology and adhesion.

scholarly journals Selective sweep for an enhancer involucrin allele identifies skin barrier adaptation out of Africa

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mary Elizabeth Mathyer ◽  
Erin A. Brettmann ◽  
Alina D. Schmidt ◽  
Zane A. Goodwin ◽  
Inez Y. Oh ◽  
...  
Keyword(s):  
Selective Sweep ◽  
Skin Barrier ◽  
Human Migration ◽  
Epidermal Differentiation ◽  
Human Populations ◽  
Epidermal Differentiation Complex ◽  
Regulatory Module ◽  
Reporter Assays ◽  
Out Of Africa

AbstractThe genetic modules that contribute to human evolution are poorly understood. Here we investigate positive selection in the Epidermal Differentiation Complex locus for skin barrier adaptation in diverse HapMap human populations (CEU, JPT/CHB, and YRI). Using Composite of Multiple Signals and iSAFE, we identify selective sweeps for LCE1A-SMCP and involucrin (IVL) haplotypes associated with human migration out-of-Africa, reaching near fixation in European populations. CEU-IVL is associated with increased IVL expression and a known epidermis-specific enhancer. CRISPR/Cas9 deletion of the orthologous mouse enhancer in vivo reveals a functional requirement for the enhancer to regulate Ivl expression in cis. Reporter assays confirm increased regulatory and additive enhancer effects of CEU-specific polymorphisms identified at predicted IRF1 and NFIC binding sites in the IVL enhancer (rs4845327) and its promoter (rs1854779). Together, our results identify a selective sweep for a cis regulatory module for CEU-IVL, highlighting human skin barrier evolution for increased IVL expression out-of-Africa.

scholarly journals Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3174
Author(s):  
Nhung Quynh Do ◽  
Shengdao Zheng ◽  
Bom Park ◽  
Quynh T. N. Nguyen ◽  
Bo-Ram Choi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
High Glucose ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Human Keratinocytes ◽  
Related Factor ◽  
Nuclear Factor ◽  
Fruit Extract ◽  
Activated T Cells

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

scholarly journals Involvement of transcribed lncRNA uc.291 and SWI/SNF complex in cutaneous squamous cell carcinoma

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
M. Mancini ◽  
A. Cappello ◽  
R. Pecorari ◽  
A. M. Lena ◽  
M. Montanaro ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Expression Patterns ◽  
Chromatin Accessibility ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Epidermal Differentiation ◽  
Differentiation Process ◽  
Clinical Biomarkers ◽  
Epidermal Differentiation Complex

AbstractWhile non-melanoma skin cancers (NMSCs) are the most common tumours in humans, only the sub-type cutaneous squamous cell carcinoma (cSCC), might become metastatic with high lethality. We have recently identified a regulatory pathway involving the lncRNA transcript uc.291 in controlling the expression of epidermal differentiation complex genes via the interaction with ACTL6A, a component of the chromatin remodelling complex SWI/SNF. Since transcribed ultra-conserved regions (T-UCRs) are expressed in normal tissues and are deregulated in tumorigenesis, here we hypothesize a potential role for dysregulation of this axis in cSCC, accounting for the de-differentiation process observed in aggressive poorly differentiated cutaneous carcinomas. We therefore analysed their expression patterns in human tumour biopsies at mRNA and protein levels. The results suggest that by altering chromatin accessibility of the epidermal differentiation complex genes, down-regulation of uc.291 and BRG1 expression contribute to the de-differentiation process seen in keratinocyte malignancy. This provides future direction for the identification of clinical biomarkers in cutaneous SCC. Analysis of publicly available data sets indicates that the above may also be a general feature for SCCs of different origins.

scholarly journals Regulation of the Dynamic Chromatin Architecture of the Epidermal Differentiation Complex Is Mediated by a c-Jun/AP-1-Modulated Enhancer

2014 ◽  
Vol 134 (9) ◽  
pp. 2371-2380 ◽  
Author(s):  
Inez Y. Oh ◽  
Danielle M. Albea ◽  
Zane A. Goodwin ◽  
Ashley M. Quiggle ◽  
Breeana P. Baker ◽  
...  
Keyword(s):  
Epidermal Differentiation ◽  
Chromatin Architecture ◽  
Epidermal Differentiation Complex

Genetic Analysis of the Epidermal Differentiation Complex (EDC) on Human Chromosome 1q21: Chromosomal Orientation, New Markers, and a 6-Mb YAC Contig

Genomics ◽  
1996 ◽  
Vol 37 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Ingo Marenholz ◽  
Armin Volz ◽  
Andreas Ziegler ◽  
Angela Davies ◽  
Ioannis Ragoussis ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Human Chromosome ◽  
Epidermal Differentiation ◽  
Epidermal Differentiation Complex ◽  
Yac Contig ◽  
Chromosome 1Q21

Murine peptidoglycan recognition proteins PglyrpIα and PglyrpIβ are encoded in the epidermal differentiation complex and are expressed in epidermal and hematopoietic tissues

Genomics ◽  
2004 ◽  
Vol 83 (6) ◽  
pp. 1151-1163 ◽  
Author(s):  
Punam Mathur ◽  
Beth Murray ◽  
Thomas Crowell ◽  
Humphrey Gardner ◽  
Normand Allaire ◽  
...  
Keyword(s):  
Epidermal Differentiation ◽  
Epidermal Differentiation Complex

scholarly journals PML Regulates the Epidermal Differentiation Complex and Skin Morphogenesis during Mouse Embryogenesis

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1130
Author(s):  
Anna Połeć ◽  
Alexander D. Rowe ◽  
Pernille Blicher ◽  
Rajikala Suganthan ◽  
Magnar Bjørås ◽  
...  
Keyword(s):  
Gene Expression ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Growth Control ◽  
Wild Type Mouse ◽  
Global Gene Expression ◽  
Mouse Embryos ◽  
Epidermal Differentiation ◽  
Envelope Gene ◽  
Epidermal Differentiation Complex

The promyelocytic leukemia (PML) protein is an essential component of nuclear compartments called PML bodies. This protein participates in several cellular processes, including growth control, senescence, apoptosis, and differentiation. Previous studies have suggested that PML regulates gene expression at a subset of loci through a function in chromatin remodeling. Here we have studied global gene expression patterns in mouse embryonic skin derived from Pml depleted and wild type mouse embryos. Differential gene expression analysis at different developmental stages revealed a key role of PML in regulating genes involved in epidermal stratification. In particular, we observed dysregulation of the late cornified envelope gene cluster, which is a sub-region of the epidermal differentiation complex. In agreement with these data, PML body numbers are elevated in basal keratinocytes during embryogenesis, and we observed reduced epidermal thickness and defective hair follicle development in PML depleted mouse embryos.

scholarly journals The Effect of Single CpG Demethylation on the Pattern of DNA-Protein Binding

2019 ◽  
Vol 20 (4) ◽  
pp. 914 ◽  
Author(s):  
Barbara Sobiak ◽  
Wiesława Leśniak
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Splicing Factors ◽  
Targeted Next Generation Sequencing ◽  
Factors Analysis ◽  
Epidermal Differentiation Complex ◽  
Complex Process ◽  
Next Generation Sequencing Ngs

Epidermal differentiation is a complex process and its regulation may involve epigenetic factors. Analysis of DNA methylation in 20 selected regions within the epidermal differentiation complex (EDC) gene cluster by targeted next-generation sequencing (NGS) detected no or only minor changes in methylation, mostly slight demethylation, occurring during the course of keratinocyte differentiation. However, a single CpG pair within the exon of the PGLYRP3 gene underwent a pronounced demethylation concomitant with an increase in PGLYRP3 expression. We have employed a DNA-affinity precipitation assay (DAPA) and mass spectrometry to examine changes in the composition of proteins that bind to DNA containing either methylated or unmethylated CpG. We found that the unmethylated probe attracted mostly RNA binding proteins, including splicing factors, which suggests that demethylation of this particular CpG may facilitate PGLYRP3 transcription and/or pre-mRNA splicing.

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