scholarly journals Temporally controlled targeted somatic mutagenesis in embryonic surfaceectoderm and fetal epidermal keratinocytes unveils two distinct developmentalfunctions of BRG1 in limb morphogenesis and skin barrier formation

Development ◽  
2005 ◽  
Vol 132 (20) ◽  
pp. 4533-4544 ◽  
Author(s):  
A. K. Indra ◽  
V. Dupe ◽  
J.-M. Bornert ◽  
N. Messaddeq ◽  
M. Yaniv ◽  
...  
Keyword(s):  
Skin Barrier ◽  
Epidermal Keratinocytes ◽  
Barrier Formation ◽  
Limb Morphogenesis ◽  
Somatic Mutagenesis

scholarly journals EGFR inhibitors switch keratinocytes from a proliferative to a differentiative phenotype affecting epidermal development and barrier function

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nicolas Joly-Tonetti ◽  
Thomas Ondet ◽  
Mario Monshouwer ◽  
Georgios N. Stamatas
Keyword(s):  
Growth Factor ◽  
Barrier Function ◽  
Kinase Inhibitors ◽  
Treatment Protocol ◽  
Growth Factor Receptor ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Epidermal Keratinocytes ◽  
Epidermal Structure

Abstract Background Cutaneous adverse drug reactions (CADR) associated with oncology therapy involve 45–100% of patients receiving kinase inhibitors. Such adverse reactions may include skin inflammation, infection, pruritus and dryness, symptoms that can significantly affect the patient’s quality of life. To prevent severe skin damages dose adjustment or drug discontinuation is often required, interfering with the prescribed oncology treatment protocol. This is particularly the case of Epidermal Growth Factor Receptor inhibitors (EGFRi) targeting carcinomas. Since the EGFR pathway is pivotal for epidermal keratinocytes, it is reasonable to hypothesize that EGFRi also affect these cells and therefore interfere with the epidermal structure formation and skin barrier function. Methods To test this hypothesis, the effects of EGFRi and Vascular Endothelial Growth Factor Receptor inhibitors (VEGFRi) at therapeutically relevant concentrations (3, 10, 30, 100 nM) were assessed on proliferation and differentiation markers of human keratinocytes in a novel 3D micro-epidermis tissue culture model. Results EGFRi directly affect basal keratinocyte growth, leading to tissue size reduction and switching keratinocytes from a proliferative to a differentiative phenotype, as evidenced by decreased Ki67 staining and increased filaggrin, desmoglein-1 and involucrin expression compared to control. These effects lead to skin barrier impairment, which can be observed in a reconstructed human epidermis model showing a decrease in trans-epidermal water loss rates. On the other hand, pan-kinase inhibitors mainly targeting VEGFR barely affect keratinocyte differentiation and rather promote a proliferative phenotype. Conclusions This study contributes to the mechanistic understanding of the clinically observed CADR during therapy with EGFRi. These in vitro results suggest a specific mode of action of EGFRi by directly affecting keratinocyte growth and barrier function.

Epidermal keratinocytes form a functional skin barrier in the absence of Atg7 dependent autophagy

2013 ◽  
Vol 71 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Heidemarie Rossiter ◽  
Ulrich König ◽  
Caterina Barresi ◽  
Maria Buchberger ◽  
Minoo Ghannadan ◽  
...  
Keyword(s):  
Skin Barrier ◽  
Epidermal Keratinocytes

scholarly journals Keratinocyte-Specific Ablation of RIPK4 Allows Epidermal Cornification but Impairs Skin Barrier Formation

2018 ◽  
Vol 138 (6) ◽  
pp. 1268-1278 ◽  
Author(s):  
Corinne Urwyler-Rösselet ◽  
Giel Tanghe ◽  
Kirsten Leurs ◽  
Barbara Gilbert ◽  
Riet De Rycke ◽  
...  
Keyword(s):  
Skin Barrier ◽  
Barrier Formation

scholarly journals Skin permeability barrier formation by the ichthyosis-causative gene FATP4 through formation of the barrier lipid ω-O-acylceramide

2020 ◽  
Vol 117 (6) ◽  
pp. 2914-2922 ◽  
Author(s):  
Haruka Yamamoto ◽  
Miku Hattori ◽  
Walee Chamulitrat ◽  
Yusuke Ohno ◽  
Akio Kihara
Keyword(s):  
Skin Barrier ◽  
Human Keratinocytes ◽  
Skin Permeability ◽  
Permeability Barrier ◽  
Barrier Dysfunction ◽  
Causative Gene ◽  
Synthetic Pathway ◽  
Barrier Formation ◽  
Chain Lengths

The epidermis-specific lipid acylceramide plays a pivotal role in the formation of the permeability barrier in the skin; abrogation of its synthesis causes the skin disorder ichthyosis. However, the acylceramide synthetic pathway has not yet been fully elucidated: Namely, the acyl-CoA synthetase (ACS) involved in this pathway remains to be identified. Here, we hypothesized it to be encoded by FATP4/ACSVL4, the causative gene of ichthyosis prematurity syndrome (IPS). In vitro experiments revealed that FATP4 exhibits ACS activity toward an ω-hydroxy fatty acid (FA), an intermediate of the acylceramide synthetic pathway. Fatp4 knockout (KO) mice exhibited severe skin barrier dysfunction and morphological abnormalities in the epidermis. The total amount of acylceramide in Fatp4 KO mice was reduced to ∼10% of wild-type mice. Decreased levels and shortening of chain lengths were observed in the saturated, nonacylated ceramides. FA levels were not decreased in the epidermis of Fatp4 KO mice. The expression levels of the FA elongase Elovl1 were reduced in Fatp4 KO epidermis, partly accounting for the reduction and shortening of saturated, nonacylated ceramides. A decrease in acylceramide levels was also observed in human keratinocytes with FATP4 knockdown. From these results, we conclude that skin barrier dysfunction observed in IPS patients and Fatp4 KO mice is caused mainly by reduced acylceramide production. Our findings further elucidate the molecular mechanism governing acylceramide synthesis and IPS pathology.

scholarly journals Canine Epidermal Keratinocytes (CPEK) Grown in Monolayer Are Not Representative of Normal Canine Keratinocytes for Permeability Studies: Pilot Studies

2022 ◽  
Vol 9 (1) ◽  
pp. 25
Author(s):  
Rosanna Marsella ◽  
Rachel Wilkes ◽  
Kim Ahrens
Keyword(s):  
Skin Barrier ◽  
Epidermal Keratinocytes ◽  
Epithelial Permeability ◽  
Electric Resistance ◽  
Pilot Studies ◽  
Cytoplasmic Staining ◽  
Time Interaction ◽  
Normal Keratinocytes ◽  
Keratinocyte Cell ◽  
Permeability Studies

Canine progenitor epidermal keratinocytes (CPEK) are used as canine keratinocyte cell line. Their suitability for skin barrier studies is unknown. Measurement of transepithelial electric resistance (TEER) evaluates epithelial permeability. We compared TEER and tight junction (TJ) expression in CPEKs and normal keratinocytes (NK) harvested from biopsies of normal dogs. CPEKs and NK were grown until confluence (D0) and for 13 additional days. Slides were fixed on D0 and stained with ZO-1 and claudin-1 antibodies. Five images/antibody were taken, randomized and evaluated blindly by three investigators for intensity, staining location, granularity, and continuousness. Cell size and variability were evaluated. TEER increased overtime to 2000 Ohms/cm in NK, while remained around 100–150 Ohms/cm in CPEK. ANOVA showed significant effect of time (p < 0.0001), group (p < 0.0001) and group x time interaction (p < 0.0001) for TEER. Size of CPEKs was significantly (p < 0.0001) smaller and less variable (p = 0.0078) than NK. Intensity of claudin-1 staining was greater in CPEKs (p < 0.0001) while granularity was less in CPEKs (p = 0.0012). For ZO-1, cytoplasmic staining was greater in CPEK (p < 0.0001) while membrane continuousness of staining was greater in NK (p = 0.0002). We conclude that CPEKs grown in monolayer are not representative of NK for permeability studies.

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