Epigenetic and metabolic regulation of epidermal homeostasis

Wagner, Roland N.; Hofbauer, Josefina Piñón; Wally, Verena; Kofler, Barbara; Schmuth, Matthias; Rosa, Laura De; Luca, Michele De; Bauer, Johann

doi:10.1111/exd.14305

Cited by 17 publications

(11 citation statements)

References 192 publications

(228 reference statements)

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“…Micro RNAs (miRNAs), which remain untranslated, are endogenous post-transcriptional modulators of gene expression with critical functions in health and disease. Most probably, together with DNA/RNA methylation, they represent an important epigenetic factor regulating gene function (López-Jiménez and Andrés-León, 2021) (Wagner et al, 2021). There is some evidence that they might explain at least to some extent, several phenotypic variations of genodermatoses within individuals harboring the same genetic background.…”

Section: Rna-based Techniquesmentioning

confidence: 99%

“…Indeed, this pathway plays a key role in keratinocyte proliferation and differentiation and possibly in clinical HHD manifestations, as well. In EB, miRNAs play a major role in fibrosis (miR-29b and miR-145) and SCC development (miR-10b) (Wagner et al, 2021). In recessive DEB, the miR-29 levels are decreased, resulting in increased miR-29 target mRNAs, including pro-fibrotic extracellular matrix collagens.…”

Section: Rna-based Techniquesmentioning

confidence: 99%

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Challenges in Treating Genodermatoses: New Therapies at the Horizon

Morren

Legius

Giuliano³

et al. 2022

Front. Pharmacol.

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Genodermatoses are rare inherited skin diseases that frequently affect other organs. They often have marked effects on wellbeing and may cause early death. Progress in molecular genetics and translational research has unravelled many underlying pathological mechanisms, and in several disorders with high unmet need, has opened the way for the introduction of innovative treatments. One approach is to intervene where cell-signaling pathways are dysregulated, in the case of overactive pathways by the use of selective inhibitors, or when the activity of an essential factor is decreased by augmenting a molecular component to correct disequilibrium in the pathway. Where inflammatory reactions have been induced by a genetically altered protein, another possible approach is to suppress the inflammation directly. Depending on the nature of the genodermatosis, the implicated protein or even on the particular mutation, to correct the consequences or the genetic defect, may require a highly personalised stratagem. Repurposed drugs, can be used to bring about a “read through” strategy especially where the genetic defect induces premature termination codons. Sometimes the defective protein can be replaced by a normal functioning one. Cell therapies with allogeneic normal keratinocytes or fibroblasts may restore the integrity of diseased skin and allogeneic bone marrow or mesenchymal cells may additionally rescue other affected organs. Genetic engineering is expanding rapidly. The insertion of a normal functioning gene into cells of the recipient is since long explored. More recently, genome editing, allows reframing, insertion or deletion of exons or disruption of aberrantly functioning genes. There are now several examples where these stratagems are being explored in the (pre)clinical phase of therapeutic trial programmes. Another stratagem, designed to reduce the severity of a given disease involves the use of RNAi to attenuate expression of a harmful protein by decreasing abundance of the cognate transcript. Most of these strategies are short-lasting and will thus require intermittent life-long administration. In contrast, insertion of healthy copies of the relevant gene or editing the disease locus in the genome to correct harmful mutations in stem cells is more likely to induce a permanent cure. Here we discuss the potential advantages and drawbacks of applying these technologies in patients with these genetic conditions. Given the severity of many genodermatoses, prevention of transmission to future generations remains an important goal including offering reproductive choices, such as preimplantation genetic testing, which can allow selection of an unaffected embryo for transfer to the uterus.

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Section: Rna-based Techniquesmentioning

confidence: 99%

Section: Rna-based Techniquesmentioning

confidence: 99%

Challenges in Treating Genodermatoses: New Therapies at the Horizon

Morren

Legius

Giuliano³

et al. 2022

Front. Pharmacol.

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“…Основной механизм регуляции гомеостаза в эпидермисе поддерживается рядом сигнальных молекул, к которым можно отнести ретинола пальмитат, витамин D3, факторы роста и цитокины. Несомненно, что ретинола пальмитат и витамин D3 формируют баланс между пролиферацией, дифференцировкой и апоптозом в эпидермисе [3,8,54]. Их совместное применение (даже если учитывать только общую сумму их эффектов) оказывает влияние на все основные звенья защиты эпидермиса и дермы: укрепляет механическую прочность рогового слоя и дермы, стабилизирует химическую и физическую защиту, в том числе препятствует проникновению чужеродных веществ и микроорганизмов в дерму, а также снижает трансэпидермальную потерю воды и электролитов, уменьшает повреждающее действие УФ и увеличивает антимикробную защиту [29,33,35,44].…”

Section: совместные эффекты жирорастворимых витаминов в составе мази ...unclassified

Barrier function of the skin and the role of fat-soluble vitamins in the correction of its disorders

Petrova

Albanova

2022

Vestnik dermatologii i venerologii

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The main function of the skin is to protect the body from negative environmental influences. The physical barrier permeability is mainly represented by the stratum corneum; however, other layers of the epidermis and the dermis are its important components. The mechanical strength of the skin is provided by intercellular contacts in the epidermis and structural proteins of the dermis. The chemical-biological barrier includes lipids, acids, natural moisturizing factor and antimicrobial peptides. Mucosal immunity system creates a barrier against infection. The microflora of healthy skin counteracts its colonization by pathogens and is vital for its immune functions. Physiological processes in the skin are closely related. A violation in one of them often leads to the formation of a whole cascade of pathological reactions affecting all the links of its protection. Vitamins A, D and E are used to correct impaired barrier function of the skin. The most pronounced effect of vitamin A (retinol palmitate) is the proliferation of epidermal cells and synthesis of extracellular matrix structures of the dermis; vitamin D (cholecalciferol) regulation of differentiation and suppression of excessive proliferation of keratinocytes; vitamin E (tocopherol acetate) antioxidant effect. The combined use of these vitamins in the composition of RadevitActive ointment affects all the main elements of the protection of the epidermis and dermis: strengthens the mechanical strength of the stratum corneum and dermis, stabilizes chemical and physical protection, including prevents the penetration of foreign substances and microorganisms, reduces transepidermal loss of water and electrolytes, reduces the damaging effect of UV, increases antimicrobial and antioxidant protection.

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“…27 In this issue, Johann Bauer and colleagues provide a broad review of epigenetic and metabolic regulatory mechanisms in epidermal homeostasis. 28 The authors also discuss exciting developments in the treatment of Epidermolysis Bullosa using epidermal stem cell transplantation. The ability of stem cells to repopulate the epidermis may depend on the underlying epigenetic landscape and as those changes become better understood new epigenetic-based methods may become available to increase the regenerative potential of epidermal stem cells.…”

Section: Epidermal Homeos Ta S Is and D Ifferentiati Onmentioning

confidence: 99%

Skin epigenetics

Andersen

Millar

2021

Experimental Dermatology

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The study of skin epigenetics is essential in understanding the mechanisms involved in cutaneous development, homeostasis and disease, and holds great promise for the identification of new therapeutic approaches to both common and rare diseases of the skin.In the current issue of Experimental Dermatology, we highlight this critically important area of research and the most exciting findings by providing a collection of state-of-the-art research articles and critical reviews of the recent literature.

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Epigenetic and metabolic regulation of epidermal homeostasis

Cited by 17 publications

References 192 publications

Challenges in Treating Genodermatoses: New Therapies at the Horizon

Challenges in Treating Genodermatoses: New Therapies at the Horizon

Barrier function of the skin and the role of fat-soluble vitamins in the correction of its disorders

Skin epigenetics

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