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

2019 ◽  
Vol 139 (5) ◽  
pp. 1010-1022 ◽  
Author(s):  
Akiko Sumitomo ◽  
Ratklao Siriwach ◽  
Dean Thumkeo ◽  
Kentaro Ito ◽  
Ryota Nakagawa ◽  
...  
Keyword(s):  
Barrier Function ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function

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.

scholarly journals Physiological Effects of Manganese Gluconate and Calcium Combination from Saint-Gervais Mont Blanc Spring Water for Human Keratinocytes Differentiation

2021 ◽  
Vol 7 (2) ◽  
pp. 1-6
Author(s):  
Franck Juchaux ◽  
Keyword(s):  
Barrier Function ◽  
Skin Barrier ◽  
Human Keratinocytes ◽  
Spring Water ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Transglutaminase 1

Alterations of skin barrier function affect quality of life and there is a need to develop dermatological/cosmetic treatments to reinforce or restore it. Inspiring of Hailey-Hailey disease, in which barrier alteration is due to a mutation of a Calcium-transporting protein (ATP2C1), we focused on the role of minerals and more especially those contained in Saint-Gervais Mont Blanc (SGMB) spring water to reinforce barrier function. Objectives: Demonstrate the interest to enrich SGMB spring water with manganese to improve both keratinocytes differentiation and barrier function. Methods: Effects of treatments on the expression of ATP2C1 and on the expression of key markers in keratinocyte differentiation and barrier function were studied by gene expression analysis on keratinocytes monolayers and also by measuring the protein expression of transglutaminase 1 using in situ immunofluorescence and image analysis in keratinocytes monolayers. Results: SGMB spring water stimulates transcriptomic expression of key markers involved in keratinocytes differentiation and barrier function while manganese gluconate has no effect. Combination of both dramatically enhances keratinocytes differentiation, in a synergistic way, at both transcriptomic and protein level. None of treatments modulated ATP2C1 expression. Conclusion: These results highlight the interest to enrich SGMB spring water with manganese to boost keratinocytes differentiation and barrier function.

scholarly journals Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model

Allergy ◽  
2012 ◽  
Vol 68 (1) ◽  
pp. 37-47 ◽  
Author(s):  
M. Gschwandtner ◽  
M. Mildner ◽  
V. Mlitz ◽  
F. Gruber ◽  
L. Eckhart ◽  
...  
Keyword(s):  
Human Skin ◽  
Barrier Function ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Skin Model ◽  
Epidermal Keratinocyte

scholarly journals In Vitro Effects of Dehydrotrametenolic Acid on Skin Barrier Function

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4583 ◽  
Author(s):  
Eunju Choi ◽  
Young-Gyu Kang ◽  
So-Hyeon Hwang ◽  
Jin Kyeong Kim ◽  
Yong Deog Hong ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Barrier Function ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Luciferase Reporter ◽  
Skin Barrier Function ◽  
Hacat Cells ◽  
Differentiation Markers ◽  
Triterpene Acid

Dehydrotrametenolic acid (DTA) is a lanostane-type triterpene acid isolated from Poria cocos Wolf (Polyporaceae). Several studies have reported the anti-inflammatory and antidiabetic effects of DTA; however, its effects on the skin are poorly understood. In this study, we investigated the effects of DTA on skin barrier function in vitro and its regulatory mechanism in human keratinocyte cell line HaCaT cells. DTA increased the microRNA (mRNA) expression of natural moisturizing factor-related genes, such as HAS-2, HAS-3, and AQP3 in HaCaT cells. DTA also upregulated the mRNA expression of various keratinocyte differentiation markers, including TGM-1, involucrin, and caspase-14. Moreover, the protein expression of HAS-2, HAS-3, and TGM-2 were significantly increased by DTA. To examine the regulatory mechanisms of DTA, Western blotting, luciferase-reporter assays, and RT-PCR were conducted. The phosphorylation of mitogen-activated protein kinases (MAPKs) and IκBα were increased in DTA-treated HaCaT cells. In addition, AP-1 and NF-κB transcriptional factors were dose-dependently activated by DTA. Taken together, our in vitro mechanism studies indicate that the regulatory effects of DTA on skin hydration and keratinocyte differentiation are mediated by the MAPK/AP-1 and IκBα/NF-κB pathways. In addition, DTA could be a promising ingredient in cosmetics for moisturizing and increased skin barrier function.

scholarly journals A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hanil Lee ◽  
Eun-Jeong Choi ◽  
Eun Jung Kim ◽  
Eui Dong Son ◽  
Hyoung-June Kim ◽  
...  
Keyword(s):  
Barrier Function ◽  
Nuclear Translocation ◽  
Clinical Investigation ◽  
Therapeutic Option ◽  
Skin Barrier ◽  
Keratinocyte Differentiation ◽  
Skin Barrier Function ◽  
Epidermal Keratinocytes ◽  
Barrier Dysfunction ◽  
Mineralocorticoid Receptor Antagonist

AbstractExcess glucocorticoids (GCs) with either endogenous or exogenous origins deteriorate skin barrier function. GCs bind to mineralocorticoid and GC receptors (MRs and GRs) in normal human epidermal keratinocytes (NHEKs). Inappropriate MR activation by GCs mediates various GC-induced cutaneous adverse events. We examined whether MR antagonists can ameliorate GC-mediated skin barrier dysfunction in NHEKs, reconstructed human epidermis (RHE), and subjects under psychological stress (PS). In a preliminary clinical investigation, topical MR antagonists improved skin barrier function in topical GC-treated subjects. In NHEKs, cortisol induced nuclear translocation of GR and MR, and GR and MR antagonists inhibited cortisol-induced reductions of keratinocyte differentiation. We identified 7,3’,4’-trihydroxyisoflavone (7,3’,4’-THIF) as a novel compound that inhibits MR transcriptional activity by screening 30 cosmetic compounds. 7,3’,4’-THIF ameliorated the cortisol effect which decreases keratinocyte differentiation in NHEKs and RHE. In a clinical study on PS subjects, 7,3',4'-THIF (0.1%)-containing cream improved skin barrier function, including skin surface pH, barrier recovery rate, and stratum corneum lipids. In conclusion, skin barrier dysfunction owing to excess GC is mediated by MR and GR; thus, it could be prevented by treatment with MR antagonists. Therefore, topical MR antagonists are a promising therapeutic option for skin barrier dysfunction after topical GC treatment or PS.

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