scholarly journals Perspective: Controlling Epidermal Terminal Differentiation with Transcriptional Bursting and RNA Bodies

2020 ◽  
Vol 8 (4) ◽  
pp. 29
Author(s):  
Duncan Wotherspoon ◽  
Clare Rogerson ◽  
Ryan F.L. O’Shaughnessy

The outer layer of the skin, the epidermis, is the principal barrier to the external environment: post-mitotic cells terminally differentiate to form a tough outer cornified layer of enucleate and flattened cells that confer the majority of skin barrier function. Nuclear degradation is required for correct cornified envelope formation. This process requires mRNA translation during the process of nuclear destruction. In this review and perspective, we address the biology of transcriptional bursting and the formation of ribonuclear particles in model organisms including mammals, and then examine the evidence that these phenomena occur as part of epidermal terminal differentiation.

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4372
Author(s):  
Kyoungmi Jung ◽  
Seung-Hun Kim ◽  
Kyung-Mi Joo ◽  
Sung-Hwan Lim ◽  
Jin-Hee Shin ◽  
...  

The stratum corneum (SC) is the outermost layer of the epidermis and plays an important role in maintaining skin moisture and protecting the skin from the external environment. Ceramide and natural moisturizing factor (NMF) are the major SC components that maintain skin moisture. In this study, we investigated whether the oral intake of enzymatically decomposed AP collagen peptides (APCPs) can improve skin moisture and barrier function by assessing changes in the ceramide and NMF contents in the SC after APCP ingestion with the aim to develop a skin functional food. Fifty participants orally ingested APCP (1000 mg) or placebo for 12 weeks, and then, skin hydration and skin texture were evaluated. SC samples were collected to analyze skin scaling, ceramide, and NMF contents. Participants in the APCP group exhibited improved skin moisture content by 7.33% (p = 0.031) and roughness by −4.09% (p = 0.036) when compared with those in the placebo group. NMF content; the amounts of amino acids (AA), including glycine and proline; and AA derivatives were significantly increased in the APCP group (31.98 μg/mg protein) compared to those in the placebo group (−16.01 μg/mg protein) (p = 0.006). The amounts of total ceramides and ceramide subclasses were significantly higher in the APCP group than in the placebo group (p = 0.014). In conclusion, our results demonstrate that APCP intake improves skin moisture and increase the ceramide and NMF contents in the SC, thereby enhancing the skin barrier function.


2007 ◽  
Vol 179 (7) ◽  
pp. 1599-1612 ◽  
Author(s):  
Lisa M. Sevilla ◽  
Rachida Nachat ◽  
Karen R. Groot ◽  
John F. Klement ◽  
Jouni Uitto ◽  
...  

The cornified envelope is assembled from transglutaminase cross-linked proteins and lipids in the outermost epidermal layers and is essential for skin barrier function. Involucrin, envoplakin, and periplakin form the protein scaffold on which the envelope assembles. To examine their combined function, we generated mice deficient in all three genes. The triple knockouts have delayed embryonic barrier formation and postnatal hyperkeratosis (abnormal accumulation of cornified cells) resulting from impaired desquamation. Cornified envelopes form but are ultrastructurally abnormal, with reduced lipid content and decreased mechanical integrity. Expression of proteases is reduced and the protease inhibitor, serpina1b, is highly upregulated, resulting in defective filaggrin processing and delayed degradation of desmoglein 1 and corneodesmosin. There is infiltration of CD4+ T cells and a reduction in resident γδ+ T cells, reminiscent of atopic dermatitis. Thus, combined loss of the cornified envelope proteins not only impairs the epidermal barrier, but also changes the composition of T cell subpopulations in the skin.


2020 ◽  
Vol 99 (6) ◽  
pp. 155-162
Author(s):  
O.B. Tamrazova ◽  
◽  
S.P. Seleznev ◽  
A.V. Tamrazova ◽  
◽  
...  

The article provides general information about the skin physiology of newborns and infants. Structural features of the skin and main adaptive shifts in newborns, are described. Тhe child has an increase in the skin barrier function of the skin, which prevents transepidermal water loss; active synthesis of natural moisturizing factor (NMF) components that control skin hydration; shift of pH to acidic environment; normalization of thermoregulatory functions; enhancement of the photoprotective function; immune restructuring for antimicrobial protection; formation of a normal microbiome. The article describes the consequences of improper skin care of a newborn, using the example of diaper dermatitis, irritant dermatitis, prickly heat and vesiculopustulosis. The importance of using specialized children's cosmetics in caring for an infant is assessed. The basic recommendations for the choice of these products are presented, where the main emphasis is on the choice of products consisting of natural ingredients. Giving preference to natural cosmetics, everyone should carefully study the composition of these products and trust the manufacturers who can guarantee safety of care products for the youngest children.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nicolas Joly-Tonetti ◽  
Thomas Ondet ◽  
Mario Monshouwer ◽  
Georgios N. Stamatas

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.


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