Stratum Corneum Maturation Research Articles

The importance of stratum corneum ω-linoleoyloxyacylceramides in human skin barrier health: their biochemistry, processing enzymes and metabolites involved in corneocyte lipid envelope maturation.

Over the past 50 years there have been great strides made in the discovery of the composition and relevance of the total stratum corneum (SC) ceramide matrix. However, the focus of this review is on the free intercellular class of ω-linoleoyloxyacylceramides, corneocyte-bound ceramides and associated lipids known as the corneocyte lipid envelope (CLE) together with their processing enzymes involved in aiding ceramide attachment the corneocyte protein envelope (CPE). Two structural models and partially shared biosynthetic pathways have been proposed for the attachment of CPE-bound O-ceramides (ω-hydroxyceramides attached to glutamate residues of proteins in the (CPE) using the 12R-lipoxygenase (12R-LOX)/epidermal lipoxygenase-3 (eLOX3)/epoxide hydrolase-3 (EPHX3)/unknown esterase/ transglutaminase-1 (TG1) attachment pathway) and CPE-bound EO-ceramides (epoxy-enone ceramides attached to cysteine residues of proteins in the CPE using the 12R-LOX/eLOX3/short chain dehydrogenase/reductase family 9C member 7 (SDR9C7)/non-enzymatic attachment pathway), i.e. there is a bifurcation step beyond epidermal eLOX3. Their formation and structures will be discussed as well as their relevance in compromised skin barrier conditions together with our own work on SC maturation examined by proteomics, lipidomics, enzyme immunolocalization studies, mechanical fragility assays and Nile red staining of corneocyte envelopes (CE). Reduced levels of 12R-LOX, eLOX3, SDR9C7 and TG1 were observed in photodamaged skin of the cheeks that were associated with reduced SC maturation as evidenced by Nile red staining and increased CE fragility. In the severely photodamaged cheeks of Albino African SC we also observed increased levels of acylceramides. Concomitantly by reducing the activity of 12R-LOX by antibody inhibition and TG1 inhibition with a known chemical inhibitor, we demonstrated in a humidity-based exvivo SC maturation model that these enzymes contributed to increased CE hydrophobicity and mechanical integrity. We hypothesize that at least the CPE-bound O-ceramide pathway is operational in the SC. Nevertheless, our understanding of the full complexity of ω-linoleoyloxyacylceramides and the composition of the CLE is limited particularly on cosmetically relevant body sites such as the face.

Three stepwise pH progressions in stratum corneum for homeostatic maintenance of the skin

The stratum corneum is the outermost skin layer with a vital role in skin barrier function. It is comprised of dead keratinocytes (corneocytes) and is known to maintain its thickness by shedding cells, although, the precise mechanisms that safeguard stratum corneum maturation and homeostasis remain unclear. Previous ex vivo studies have suggested a neutral-to-acidic pH gradient in the stratum corneum. Here, we use intravital pH imaging at single-corneocyte resolution to demonstrate that corneocytes actually undergo differentiation to develop three distinct zones in the stratum corneum, each with a distinct pH value. We identified a moderately acidic lower, an acidic middle, and a pH-neutral upper layer in the stratum corneum, with tight junctions playing a key role in their development. The upper pH neutral zone can adjust its pH according to the external environment and has a neutral pH under steady-state conditions owing to the influence of skin microbiota. The middle acidic pH zone provides a defensive barrier against pathogens. With mathematical modeling, we demonstrate the controlled protease activation of kallikrein-related peptidases on the stratum corneum surface that results in proper corneocyte shedding in desquamation. This work adds crucial information to our understanding of how stratum corneum homeostasis is maintained.

Gasdermin A Is Required for Epidermal Cornification during Skin Barrier Regeneration and in an Atopic Dermatitis-Like Model

Atopic dermatitis (AD) is featured with impaired skin barrier. The stratum corneum (SC) and the intercellular tight junctions (TJs) constitute the permeability barrier, which is essential to protect the host water loss and pathogen entrance. The epidermal barrier is constantly renewed by differentiating keratinocytes through cornification, during which autophagy contributes to organelles and nucleus elimination. The human GSDMA and its mouse homologs Gsdma1-3 are expressed in the suprabasal epidermis. Although a pyroptotic role for GSDMA/Gsdma1 in host defense against Streptococcus pyogenes has been reported, the physiological function of Gsdma1/a2/a3 in epidermal homeostasis remains elusive. Herein, through repeated epidermal barrier disruption, we found that TJ formation and SC maturation were defective in the Gsdma1/a3-deficient epidermis. Using comparative gene profiling analysis, mitochondrial respiration measurement, and in vivo tracing of mitophagy, our data indicate that Gsdma1/a3 activation leads to mitochondrial dysfunction and subsequently facilitates mitochondrial turnover and epidermal cornification. In calcipotriol (MC903)-induced AD-like animal model, we demonstrated that Gsdma1/a3-deficiency selectively enhanced the Th2 response. Remarkably, the GSDMA expression is reduced in the epidermis of patients with AD compared to normal individuals. Gsdma1/a3-deficiency might be involved in AD pathogenesis, likely through GSDMA-mediated epidermal differentiation and cornification.

Moisturizing at a molecular level - The basis of Corneocare.

This review covers the last 20 years of research we and our collaborators have conducted on ethnic differences in facial skin moisturization placed in historical context with previous research. We have focussed particularly on the biochemical and cellular gradients of the stratum corneum (SC) with the aim of discovering new skin moisturization and SC maturation mechanisms, identifying new technologies and/or providing conceptual innovations for ingredients that will improve our understanding and treatment of dry skin. Specifically, we discuss gradients for corneodesmosomes and proteases, corneocyte phenotype-inducing enzymes, filaggrin and natural moisturizing factor (NMF), and barrier lipids. These gradients are interdependent and influence greatly corneocyte maturation. The interrelationship between corneodesmolysis and the covalent attachment of ω-hydroxy ceramides and ω-hydroxy fatty acids to the corneocyte protein envelope forming the corneocyte lipid envelope is especially relevant in our new understanding of mechanisms leading to dry skin. This process is initiated by a linoleoyl-ω-acyl ceramide transforming enzyme cascade including 12R lipoxygenase (12R-LOX), epidermal lipoxygenase-3 (eLOX3), epoxide hydrolase 3 (EPHX3), short-chain dehydrogenase/reductase family 9C member 7 (SDR9C7), ceramidase and transglutaminase 1. Our research has opened the opportunity of using novel treatment systems for dry skin based on lipids, humectants, niacinamide and inhibitors of the plasminogen system. It is clear that skin moisturization is a more complex mechanism than simple skin hydration.

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice.

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

Prospective, Case-Control Study Evaluating Effects of No-Sting Liquid Barrier Film on Skin Condition and Maturation of Stratum Corneum in Premature Neonates.

To assess effects of a no-sting liquid barrier film (NSLBF) on the skin condition and maturation of the stratum corneum in premature neonates. This was a prospective, case-control study with each subject serving as their own control. The sample comprised 33 neonates, between 23 and 32 weeks of gestational age (GA). Participants received care in a level 4 neonatal intensive care unit in the northeastern United States. Data were collected between May 2018 and May 2019. All participants had NSLBF applied to their left chest, left abdomen, and left anterior and posterior upper thigh. The right side was left untreated and served as self-control. Measurements of skin pH, hydration, transepidermal water loss (TEWL) and Neonatal Skin Condition Scores were obtained on both the untreated right and treated left sides of the body over a 14-day period on days 1, 3, 7, and 14. Worsening skin condition scores were observed on the treated side on days 7 and 14. There was an improvement in TEWL on the treated side, manifested as decrease in TEWL values. There was no difference in pH. At all points in time hydration was lower on the treated side. Worsening skin condition scores and hydration status on the treated side indicate an altered or delayed process of skin maturation. These findings suggest that no-sting liquid barrier (NSLB) application should be limited to skin under medical devices, dressings, tapes, and affected areas. In addition, we recommend allowing adequate intervals to allow physiologic stratum corneum maturation between applications of NSLB.

Prospective, Case-Control Study Evaluating Effects of No-Sting Liquid Barrier Film on Skin Condition and Maturation of Stratum Corneum in Premature Neonates.

Prospective, Case-Control Study Evaluating Effects of No-Sting Liquid Barrier Film on Skin Condition and Maturation of Stratum Corneum in Premature Neonates.

Cholesterol sulfate fluidizes the sterol fraction of the stratum corneum lipid phase and increases its permeability

Desulfation of cholesterol sulfate (CholS) to cholesterol (Chol) is an important event in epidermal homeostasis and necessary for stratum corneum (SC) barrier function. The CholS/Chol ratio decreases during SC maturation but remains high in pathological conditions, such as X-linked ichthyosis, characterized by dry and scaly skin. The aim of this study was to characterize the influence of the CholS/Chol molar ratio on the structure, dynamics, and permeability of SC lipid model mixtures. We synthesized deuterated CholS and investigated lipid models with specifically deuterated components using 2H solid-state NMR spectroscopy at temperatures from 25°C to 80°C. Although the rigid acyl chains in ceramides and fatty acids remained essentially rigid upon variation of the CholS/Chol ratio, both sterols were increasingly fluidized in lipid models containing higher CholS concentrations. We also show the X-ray repeat distance of the lipid lamellar phase (105 Å) and the orthorhombic chain packing of the ceramide’s acyl chains and long free fatty acids did not change upon the variation of the CholS content. However, the Chol phase separation visible in models with high Chol concentration disappeared at the 50:50 CholS/Chol ratio. This increased fluidity resulted in higher permeabilities to model markers of these SC models. These results reveal that a high CholS/Chol ratio fluidizes the sterol fraction and increases the permeability of the SC lipid phase while maintaining the lamellar lipid arrangement with an asymmetric sterol distribution.

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

In humans, receptor-interacting protein kinase 4 (RIPK4) mutations can lead to the autosomal recessive Bartsocas-Papas and popliteal pterygium syndromes, which are characterized by severe skin defects, pterygia, as well as clefting. We show here that the epithelial fusions observed in RIPK4 full knockout (KO) mice are E-cadherin dependent, as keratinocyte-specific deletion of E-cadherin in RIPK4 full KO mice rescued the tail-to-body fusion and fusion of oral epithelia. To elucidate RIPK4 function in epidermal differentiation and development, we generated epidermis-specific RIPK4 KO mice (RIPK4EKO). In contrast to RIPK4 full KO epidermis, RIPK4EKO epidermis was normally stratified and the outside-in skin barrier in RIPK4EKO mice was largely intact at the trunk, in contrast to the skin covering the head and the outer end of the extremities. However, RIPK4EKO mice die shortly after birth due to excessive water loss because of loss of tight junction protein claudin-1 localization at the cell membrane, which results in tight junction leakiness. In contrast, mice with keratinocyte-specific RIPK4 deletion during adult life remain viable. Furthermore, our data indicate that epidermis-specific deletion of RIPK4 results in delayed keratinization and stratum corneum maturation and altered lipid organization and is thus indispensable during embryonic development for the formation of a functional inside-out epidermal barrier.

The effect of photodamage on the female Caucasian facial stratum corneum corneome using mass spectrometry-based proteomics.

The effect of photodamage on facial stratum corneum (SC) is still poorly understood. To describe the SC proteome from tape strippings of Caucasian SC from photoexposed cheek and photoprotected post-auricular (PA) site, a global analysis of photodamage on the skin will be developed leading to a better understanding of keratinocyte signalling pathways and identification of new molecular targets for the treatment of photoaged skin. Female Caucasian subjects had nine consecutive tape strippings taken from their cheeks and PA site. Proteins were extracted and the trypsin-digested peptides were analysed by nanochromatography coupled to a high-resolution mass spectrometer. Data-dependent acquisition allowed protein identification that was processed by Paragon algorithm of Protein Pilot software. Changes in the levels of epidermal differentiation proteins were apparent indicating poor epidermal differentiation and SC maturation (keratins, cornified envelope (CE) proteins) on photoexposed cheeks. Differences in protease-anti-protease balance were observed for corneodesmolysis (favouring desquamation) and filaggrinolysis (favouring reduced filaggrin processing). 12R-LOX, a CE maturation enzyme, was reduced in photodamaged skin but not transglutaminases. Changes in signal keratinocyte transduction pathway markers were demonstrated especially by reduced levels of downstream signalling markers such as calreticulin (unfolded protein response; UPR) and increased level of stratifin (target of rapamycin; mTOR). Evidence for impaired proteostasis was apparent by reduced levels of a key proteasomal subunit (subunit beta type-6). Finally, key antioxidant proteins were upregulated except catalase. Clear examples of poor keratinocyte differentiation and associated metabolic and signalling pathways together with reduced SC maturation were identified in photodamaged facial SC. Corneocyte immaturity was evident with changes in CE proteins. Particularly, the reduction in 12R-LOX is a novel finding in photodamaged skin and supports the lack of SC maturation. Moreover, filaggrinolysis was reduced, whereas corneodesmolysis was enhanced. From our results, we propose that there is a poor cross-talk between the keratinocyte endoplasmic reticulum UPR, proteasome network and autophagy machinery that possibly leads to impaired keratinocyte proteostasis. Superimposed on these aberrations is an apparently enhanced mTOR pathway that also contributes to reduced SC formation and maturation. Our results clearly indicate a corneocyte scaffold disorder in photodamaged cheek SC.

A fundamental investigation into aspects of the physiology and biochemistry of the stratum corneum in subjects with sensitive skin.

Sensitive skin is a poorly understood skin condition. Defects in stratum corneum (SC) barrier function and/or extrasensory neuronal networks in the epidermis are believed to be involved in the problem. This study aimed to unravel the relationships between bleomycin hydrolase (BH) and calpain-1 (C-1), pyrrolidone carboxylic acid (PCA) levels, corneocyte maturation, transglutaminase (TG) and plasmin activities on the cheeks of subjects with sensitive skin. Forty-eight female Caucasian subjects, Fitzpatrick skin phototypes II-III, with self-perceived sensitive facial skin, were assessed and underwent a capsaicin reactivity test. Expert grading of skin condition was conducted as well as the measurement of transepidermal water loss (TEWL), skin capacitance, SC cohesion and SC integrity. BH, C-1 and plasmin activities were measured as well as PCA levels, plasmin and TG activity. Differential Nile red and involucrin immunostaining was performed to assess corneocyte maturation and size. About 52% of the subjects reacted to capsaicin. There were no significant differences between the capsaicin-sensitive and non-capsaicin-sensitive subjects with reference to skin grading, TEWL, skin capacitance and SC cohesion. PCA levels and BH activity were lowest in the capsaicin-sensitive panel (P < 0.05) and were correlated in non-capsaicin-sensitive subjects (r = 0.72). The activity of TG was significantly lower (48%) in the capsaicin-sensitive subjects (P < 0.001) and their corneocytes were less mature and smaller (P ≤ 0.05). SC was estimated to be thinner (6.87 ± 0.28 vs. 8.68 ± 0.26 μm; P = 0.001) in the capsaicin-sensitive subjects with a corresponding shorter SC path length (83.2 ± 4.4 μm and 113.1 ± 4.5 μm; P = 0.001). Despite the physiological similarities between the two groups of sensitive skin subjects, differences in their biochemistry were clearly evident. Lower levels of PCA, BH and TG activities together with a greater number of smaller and immature corneocytes indicate inferior SC maturation in the capsaicin-sensitive subjects. The reduced maturation of corneocytes and thinner SC likely contributes to a greater penetration of capsaicin and the associated increased skin sensitivity.

Development and organization of human stratum corneum after birth: electron microscopy isotropy score and immunocytochemical corneocyte labelling as epidermal maturation's markers in infancy

There is growing evidence for the ongoing structural and functional adaptation of the skin after birth. The aim of this study was the definition of scanning electron microscopy markers of skin maturation in different age groups (birth to adulthood). We propose a semiquantitative score to analyse the maturation of the skin surface and a complementary evaluation of the distribution of corneodesmosin and corneodesmosomes. An electron microscopy isotropy (E.M.I.) score was performed in six age-groups to include fullterm neonates, babies, children and adults. The distribution of corneodesmosome remnants was analysed by corneodesmosin distribution with immunocytochemical corneocyte labelling. The E.M.I. score showed the highest anisotropy in neonates. The youngest groups displayed irregular and thick cell clusters composed of poorly individualized cells. In the older groups, the distribution of superficial corneocytes was more regular. The cells evenly covered the surface and displayed easily visualized single cell outlines. The distribution of immune-labelled corneodesmosome remnants and the corneocyte projected area showed a correlation between age and structural maturation. The observed evolution indicated a poorly controlled process of corneocyte desquamation in infants and confirmed the relative immaturity of the epidermal barrier up to 1-2 years after birth under basal conditions. Our study is the first attempt at semiquantitative evaluation of the micromorphology maturation of the epidermal surface at the ultrastructural level. The E.M.I. score and the associated pattern of corneodesmosome breakdown may be used as markers of the stratum corneum maturation.

Molecular basis for stratum corneum maturation and moisturization

This themed edition of BJD is dedicated to the work of Professor Ronald Marks for his untiring work on the understanding of stratum corneum (SC) structure and function. He and his coworkers, in my opinion, had the right focus for cosmetic dermatology issues. Namely, consumers experience the wonderful properties of the SC through sight, touch and the somatosensory system. They do not experience, for example, transepidermal water loss and skin conductance or capacitance! Marks understood this and set about developing the methodologies to examine the changes in SC architecture and function when desquamation goes haywire. More importantly, he understood that moisturizers do far more than simply hydrate the SC, as exemplified in the paper by Tree and Marks, 'An explanation for the placebo effect of bland ointment bases.' Moisturizing ingredients influence the properties of the SC in many ways with the sole purpose of overcoming the signs and symptoms of dry skin. Marks demonstrated the decrease in SC cohesion following use of hydrating agents, which led to the mechanistic work on the effects of a simple molecule like glycerol on the desquamatory process. In further exploiting forced desquamation and use of abrasion, he showed that improvements in exfoliation contribute to the mitigation of the signs of photodamaged skin, which can explain part of the antiageing effect of simple moisturizers. It is here that I should point out that at least this particular author in 1988 was 'standing on the shoulders of' a great corneologist whose work influenced his research directions. So this paper will provide an update on the latest developments for the molecular basis of SC maturation and moisturization, while highlighting the contributions of Professor Marks in the different areas.

Distribution of corneodesmosomes on superficial corneocytes differs between infants and adults: A new look at the stratum corneum maturation

Distribution of corneodesmosomes on superficial corneocytes differs between infants and adults: A new look at the stratum corneum maturation

Stratum corneum dysfunction in dandruff

SummarySynopsisDandruff is characterized by a flaky, pruritic scalp and affects up to half the world’s population post-puberty. The aetiology of dandruff is multifactorial, influenced by Malassezia, sebum production and individual susceptibility. The commensal yeast Malassezia is a strong contributory factor to dandruff formation, but the presence of Malassezia on healthy scalps indicates that Malassezia alone is not a sufficient cause. A healthy stratum corneum (SC) forms a protective barrier to prevent water loss and maintain hydration of the scalp. It also protects against external insults such as microorganisms, including Malassezia, and toxic materials. Severe or chronic barrier damage can impair proper hydration, leading to atypical epidermal proliferation, keratinocyte differentiation and SC maturation, which may underlie some dandruff symptoms. The depleted and disorganized structural lipids of the dandruff SC are consistent with the weakened barrier indicated by elevated transepidermal water loss. Further evidence of a weakened barrier in dandruff includes subclinical inflammation and higher susceptibility to topical irritants. We are proposing that disruption of the SC of the scalp may facilitate dandruff generation, in part by affecting susceptibility to metabolites from Malassezia. Treatment of dandruff with cosmetic products to directly improve SC integrity while providing effective antifungal activity may thus be beneficial.RésuméLes pellicules se caractérisent par un cuir chevelu prurigineux, squameux, et affectent jusqu’à la moitié de la population post-pubertaire du monde. L’étiologie des pellicules est multifactorielle, influencée par Malassezia, par la production de sébum, et par la susceptibilité individuelle. La levure commensale Malassezia est un facteur fortement contributif à la formation de pellicules, mais la présence de Malassezia aussi sur les cuirs chevelus sains indique que Malassezia seule n’est pas une cause suffisante. Un stratum corneum (SC) sain forme une barrière protectrice pour empêcher la perte d’eau et maintenir l’hydratation du cuir chevelu. Il protège également contre les agressions externes tels les micro-organismes, y compris Malassezia, ou des substances toxiques. Des dommages aigus ou chroniques au niveau de la barrière peuvent nuire à une bonne hydratation, conduisant à des effets atypiques de la prolifération épidermique, de la différenciation des kératinocytes, et de la maturation du SC, ce qui peut expliquer une partie des symptômes des pellicules. L’appauvrissement et la désorganisation des lipides structurels d’un stratum corneum sujet aux pellicules sont compatibles avec la notion d’une barrière affaiblie telle qu’indiquée par une perte d’eau transépidermique élevée. Une preuve supplémentaire d’une barrière affaiblie dans les cas des pellicules est fournie par un niveau d’inflammation infraclinique et une plus grande susceptibilité aux irritants topiques. Nous proposons que la perturbation du SC du cuir chevelu facilite la production de pellicules, en partie en augmentant la sensibilité aux métabolites de Malassezia. Le traitement des pellicules avec des produits cosmétiques pour améliorer directement l’intégrité du SC, tout en offrant une activité antifongique efficace peut donc être bénéfique.

Actualités sur la physiopathologie de la dermatite atopique

Atopic dermatitis (AD) is very common in industrialized countries, where it affects 15% to 30% of children and 2% to 10% of adults. AD has a complex determinism, combining environmental influences and genetic predisposition, hitherto dominated by an immunological perspective, particularly after the discovery of associated high IgE serum levels. DA is a possible mode of onset of asthma, allergic rhinitis and food allergies, resulting in the poorly understood "atopic march". The discovery of mutations in the filaggrin gene, a key protein for stratum corneum maturation, have refocused attention on the skin and operated a Copernican revolution in our understanding of this group of disorders. AD has become a prototype of inflammatory epithelial barrier diseases. The epidermal barrier has three major elements: the stratum corneum, which provides an air-liquid barrier, tight junctions in the granular layer (liquid-liquid barrier), and Langerhans cells that capture antigens (immunological barrier). Better knowledge of the molecular events underlying epidermal barrier function and its dysfunction in AD should lead to ways of preventing and eventually curing this group of disorders.

Neonatal intensive care practices and the influence on skin condition

Premature skin has a thinner epidermis with a poorly formed stratum corneum (SC) barrier compared to full term skin. Poor skin integrity increases the risk of exposure to irritants and infectious agents. Interventions that facilitate skin maturation are essential. The objective was to examine the effects of prematurity and time from birth on SC maturation and to identify factors that impact skin condition. A retrospective review was conducted among 130 NICU patients. Skin regions were evaluated for erythema, rash, integrity and function. The effects of gestational age, time from birth, stool exposure, nutrition and diagnosis were examined. Three groups emerged: (i) premature and <38 weeks adjusted age; (ii) premature and >38 weeks adjusted age; and (iii) full term. Surprisingly, the premature infants exhibited lower perineal irritation and greater SC integrity (lower transepidermal water loss) than full terms (P < 0.05). Group 2 had a longer time before the first skin-stool contact. Chest skin pH showed maturational changes for Group 1 (P < 0.05) but did not change for premature Group 2 who was older at enrollment. Erythema was lower for infants using elemental formulas or total parenteral nutrition. Premature infants with early stool contact and high exposure, full term infants, and patients with congenital diaphragmatic hernia or trisomy 21 are at high risk for skin compromise and may benefit from prophylactic interventions to minimize compromise. Low stool exposure and greater time before the first stool contact appear to be protective against skin compromise.

Skin hydration: a review on its molecular mechanisms

Water is absolutely essential for the normal functioning of the skin and especially its outer layer, the stratum corneum (SC). Loss of water from the skin must be carefully regulated, a function dependent on the complex nature of the SC. The retention of water in the SC is dependent on two major components: (1) the presence of natural hygroscopic agents within the corneocytes (collectively referred to as natural moisturizing factor) and (2) the SC intercellular lipids orderly arranged to form a barrier to transepidermal water loss (TEWL). The water content of the SC is necessary for proper SC maturation and skin desquamation. Increased TEWL impairs enzymatic functions required for normal desquamation resulting in the visible appearance of dry, flaky skin. There have been recent discoveries regarding the complex mechanisms of skin hydration. In particular, it has been discovered that glycerol, a well-known cosmetic ingredient, exists in the SC as a natural endogenous humectant. Hyaluronan, which has been regarded mainly as dermal component, is found in the epidermis and is important for maintaining normal SC structure and epidermal barrier function. More importantly, the discovery of the existence of the water-transporting protein aquaporin-3 in the viable epidermis and the presence of tight junction structures at the junction between the stratum granulosum and SC have brought new insights into the mechanisms of skin water distribution and barrier function.

The cornified cell envelope: an important marker of stratum corneum maturation in healthy and dry skin

The cornified cell envelope (CE) formed by transglutaminase-mediated epsilon-(gamma-glutamyl)lysine cross-linking of specialized corneocyte proteins is the most insoluble component of the terminally differentiated keratinocyte. Under normal Nomarski optics, two types of CE are readily distinguishable: an irregularly shaped, readily deformed 'fragile' envelope (CEf), which predominates in the deepest layers of the stratum corneum, and a polygonal "resilient" or 'rigid' envelope (CEr), which represents over 80% of the CE population in the superficial layers. This distinct spatial distribution indicates a maturation of the CE from the fragile to the resilient morphology during stratum corneum maturation. In this study, we have examined morphological and physical changes occurring in the CE during the terminal differentiation. The proportion of CEf and CEr present in superficial samples of stratum corneum were readily distinguishable following staining with Tetrarhodamine isothiocyanate (TRITC) and showed significant body site variation. The percentage of CEf was highest on samples recovered from exposed body sites (back of hand > cheek > inner arm [bicep region]) suggesting innate body site differences or that photodamage and other environmental trauma can reduce or delay normal CE maturation. Soap-induced dryness resulted in a significant decrease in CE maturation coincidental with reduced corneodesmosomal hydrolysis. Effective moisturization of winter-induced dry skin enhanced CE maturation (33% increase in TRITC fluorescence, n = 14 following 4-week treatment). Using a novel micromanipulation instrument, the force required (microN) to maximally deform individual CEf and CEr was compared. CEf recovered from deep stratum corneum were significantly softer and weaker than CEr recovered from superficial layers. These studies indicate that the normal process of CE maturation is associated with an actual strengthening of this insoluble protective structure and that the impairment of this process is associated with poor quality of the stratum corneum.

Accelerated DNA fragmentation of the denture‐bearing mucosal epithelium in an animal model of diabetes

This study examined the effect of masticatory pressure transmitted directly to the hard palate mucosa on the final stage of terminal differentiation of keratinizing system of rats with and without streptozotocin-induced diabetes mellitus. In the nondiabetic rats with masticatory pressure, the number of terminal-deoxynucleotidyl-transferase-mediated deoxyuridine-triphospate-biotin nick end labelling (TUNEL) positive cells tended to increase about twice as much as in the nondiabetic rats without pressure with and without denture. A similar tendency of increase was observed in the diabetic rats without pressure. The synergy of the mechanical pressure and diabetic condition for 2 weeks greatly accelerated the DNA fragmentation, showing 8-fold increase in TUNEL positive cells over the normal control, and caused exfoliation of the stratum corneum. A 4-week exposure of diabetics to the masticatory pressure induced laminar splitting in the midst of the spinosum. Some cells in the stratum granulosum exhibited a sign of DNA fragmentation when laminar splitting took place in the vital cell layer. Premature DNA fragmentation may disturb the adhesion between spinosum cells and prevent the maturation of stratum corneum. Increase in Bax protein-like immunoreactivity in these epithelial cells as revealed by immunocytochemistry may underlie the premature DNA fragmentation in the oral masticatory epithelium under pressure in diabetic patients.