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Special Issue "Skin Epidermis and Barrier Function"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2020).

Special Issue Editor

Prof. Dr. Kyung-Min Lim
E-Mail
Guest Editor
College of Pharmacy, Ewha Womans University, Seoul, Korea
Interests: skin; cosmetics; whitening; anti-aging; atopic dermatitis; alternative to animal test methods; irritation
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Skin epidermis is the outermost epithelial tissue that protects our body from the outer environment. Human skin epidermis has evolved to form an effective barrier against obnoxious stimuli from outside entering into the body and loss of moisture within to the outer environment. Complex differentiation/proliferation processes orchestrate the maturation of skin epidermis, and various molecules participate in skin barrier function. Disruption of epidermal homeostasis is closely linked with various skin diseases that include xerosis, atopic dermatitis, psoriasis, and skin squamous cell carcinoma. Consequently, skin epidermis has been an important topic for dermatology, pathology, pharmacology, toxicology, molecular biology, and the cosmetic sciences. This Special Issue under the title of “Skin Epidermis and Barrier Function” invites excellent research related to various aspects of skin epidermis and barrier function at molecular level.

Prof. Dr. Kyung-Min Lim
Guest Editor

Manuscript Submission Information

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Keywords

  • Skin epidermis
  • Stratum corneum
  • Corneocytes, keratinocytes
  • Epidermal differentiation/proliferation
  • Skin barrier function, skin barrier dysfunction
  • Epidermal lipids, ceramide, free fatty acid, cholesterol, natural moisturizing factor
  • Filaggrin, loricrin, involucrin, keratin, corneodesmosome
  • Tight junction
  • Atopic dermatitis, Eczema
  • Dry skin, Psoriasis
  • Squamous cell carcinoma
  • Skin stem cell

Published Papers (14 papers)

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Editorial

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Editorial
Skin Epidermis and Barrier Function
Int. J. Mol. Sci. 2021, 22(6), 3035; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22063035 - 16 Mar 2021
Viewed by 445
Abstract
The skin epidermis is the outermost epithelial tissue that protects the body from the external environment [...] Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)

Research

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Article
hiPSC-Derived Epidermal Keratinocytes from Ichthyosis Patients Show Altered Expression of Cornification Markers
Int. J. Mol. Sci. 2021, 22(4), 1785; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041785 - 11 Feb 2021
Cited by 1 | Viewed by 562
Abstract
Inherited ichthyoses represent a large heterogeneous group of skin disorders characterised by impaired epidermal barrier function and disturbed cornification. Current knowledge about disease mechanisms has been uncovered mainly through the use of mouse models or human skin organotypic models. However, most mouse lines [...] Read more.
Inherited ichthyoses represent a large heterogeneous group of skin disorders characterised by impaired epidermal barrier function and disturbed cornification. Current knowledge about disease mechanisms has been uncovered mainly through the use of mouse models or human skin organotypic models. However, most mouse lines suffer from severe epidermal barrier defects causing neonatal death and human keratinocytes have very limited proliferation ability in vitro. Therefore, the development of disease models based on patient derived human induced pluripotent stem cells (hiPSCs) is highly relevant. For this purpose, we have generated hiPSCs from patients with congenital ichthyosis, either non-syndromic autosomal recessive congenital ichthyosis (ARCI) or the ichthyosis syndrome trichothiodystrophy (TTD). hiPSCs were successfully differentiated into basal keratinocyte-like cells (hiPSC-bKs), with high expression of epidermal keratins. In the presence of higher calcium concentrations, terminal differentiation of hiPSC-bKs was induced and markers KRT1 and IVL expressed. TTD1 hiPSC-bKs showed reduced expression of FLG, SPRR2B and lipoxygenase genes. ARCI hiPSC-bKs showed more severe defects, with downregulation of several cornification genes. The application of hiPSC technology to TTD1 and ARCI demonstrates the successful generation of in vitro models mimicking the disease phenotypes, proving a valuable system both for further molecular investigations and drug development for ichthyosis patients. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Article
Ex Vivo Live Full-Thickness Porcine Skin Model as a Versatile In Vitro Testing Method for Skin Barrier Research
Int. J. Mol. Sci. 2021, 22(2), 657; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020657 - 11 Jan 2021
Cited by 1 | Viewed by 832
Abstract
Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model [...] Read more.
Since the European Union (EU) announced their animal testing ban in 2013, all animal experiments related to cosmetics have been prohibited, creating a demand for alternatives to animal experiments for skin studies. Here, we investigated whether an ex vivo live porcine skin model can be employed to study the safety and skin barrier-improving effects of hydroxyacids widely used in cosmetics for keratolytic peels. Glycolic acid (1–10%), salicylic acid (0.2–2%), and lactobionic acid (1.2–12%) were used as representative substances for α-hydroxyacid (AHA), β-hydroxyacid (BHA), and polyhydroxyacid (PHA), respectively. When hydroxyacids were applied at high concentrations on the porcine skin every other day for 6 days, tissue viability was reduced to 50–80%, suggesting that the toxicity of cosmetic ingredients can be evaluated with this model. Based on tissue viability, the treatment scheme was changed to a single exposure for 20 min. The protective effects of a single exposure of hydroxyacids on skin barrier function were evaluated by examining rhodamine permeability and epidermal structural components of barrier function using immunohistochemistry (IHC) and immunofluorescence (IF) staining. Lactobionic acid (PHAs) improved skin barrier function most compared to other AHAs and BHAs. Most importantly, trans-epidermal water loss (TEWL), an important functional marker of skin barrier function, could be measured with this model, which confirmed the significant skin barrier-protective effects of PHAs. Collectively, we demonstrated that the ex vivo live full-thickness porcine skin model can be an excellent alternative to animal experiments for skin studies on the safety and efficacy of cosmetic ingredients. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Article
miR-155 Contributes to Normal Keratinocyte Differentiation and Is Upregulated in the Epidermis of Psoriatic Skin Lesions
Int. J. Mol. Sci. 2020, 21(23), 9288; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239288 - 05 Dec 2020
Cited by 3 | Viewed by 485
Abstract
The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA–miRNA networks of KCs at different stages [...] Read more.
The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA–miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1β and INFγ synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Article
Effects of Tenascin C on the Integrity of Extracellular Matrix and Skin Aging
Int. J. Mol. Sci. 2020, 21(22), 8693; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228693 - 18 Nov 2020
Cited by 2 | Viewed by 845
Abstract
Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the [...] Read more.
Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. In this study, we found that the Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of transforming growth factor-β1 (TGF-β1) mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Article
Weak Ultraviolet B Enhances the Mislocalization of Claudin-1 Mediated by Nitric Oxide and Peroxynitrite Production in Human Keratinocyte-Derived HaCaT Cells
Int. J. Mol. Sci. 2020, 21(19), 7138; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197138 - 27 Sep 2020
Cited by 3 | Viewed by 717
Abstract
A tight junction (TJ) makes a physical barrier in the epidermal cells of skin. Ultraviolet (UV) light may disrupt the TJ barrier, but the mechanism has not been well clarified. Weak UVB (5 mJ/cm2) caused mislocalization of claudin-1 (CLDN1), a component [...] Read more.
A tight junction (TJ) makes a physical barrier in the epidermal cells of skin. Ultraviolet (UV) light may disrupt the TJ barrier, but the mechanism has not been well clarified. Weak UVB (5 mJ/cm2) caused mislocalization of claudin-1 (CLDN1), a component of the TJ strand, and disruption of TJ barrier in human keratinocyte-derived HaCaT cells. The UVB-induced mislocalization of CLDN1 was inhibited by monodansylcadaverine (MDC), a clathrin-dependent endocytosis inhibitor, suggesting that UVB enhances the internalization of CLDN1. Transepidermal electrical resistance and paracellular flux of lucifer yellow, a fluorescent hydrophilic marker, were rescued by MDC. UVB changed neither the total nor phosphorylation levels of CLDN1, but it increased both mono-ubiquitination and tyrosine nitration levels of CLDN1. Fluorescence measurements revealed that UVB increased intracellular free Ca2+, nitric oxide (NO), and peroxynitrite contents, which were inhibited by Opsin2 (OPN2) siRNA, suggesting that OPN2 functions as a UVB sensor. The effects of UVB were inhibited by an antagonist of transient receptor potential type vanilloid 1 (TRPV1) and Ca2+ chelator. Both NO donor and peroxynitrite donor induced the mislocalization of CLDN1 and disruption of TJ barrier, which were rescued by a NO synthase (NOS) inhibitor and a peroxynitrite scavenger. Weak UVB irradiation induced the disruption of TJ barrier mediated by mislocalization of CLDN1 in HaCaT cells. The OPN2/TRPV1/NOS signaling pathway may be a novel target for preventing destruction of the TJ barrier by UVB irradiation. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Article
Synthetic Retinoid Seletinoid G Improves Skin Barrier Function through Wound Healing and Collagen Realignment in Human Skin Equivalents
Int. J. Mol. Sci. 2020, 21(9), 3198; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21093198 - 30 Apr 2020
Cited by 7 | Viewed by 1217
Abstract
The outer epidermal skin is a primary barrier that protects the body from extrinsic factors, such as ultraviolet (UV) radiation, chemicals and pollutants. The complete epithelialization of a wound by keratinocytes is essential for restoring the barrier function of the skin. However, age-related [...] Read more.
The outer epidermal skin is a primary barrier that protects the body from extrinsic factors, such as ultraviolet (UV) radiation, chemicals and pollutants. The complete epithelialization of a wound by keratinocytes is essential for restoring the barrier function of the skin. However, age-related alterations predispose the elderly to impaired wound healing. Therefore, wound-healing efficacy could be also considered as a potent function of an anti-aging reagent. Here, we examine the epidermal wound-healing efficacy of the fourth-generation retinoid, seletinoid G, using HaCaT keratinocytes and skin tissues. We found that seletinoid G promoted the proliferation and migration of keratinocytes in scratch assays and time-lapse imaging. It also increased the gene expression levels of several keratinocyte proliferation-regulating factors. In human skin equivalents, seletinoid G accelerated epidermal wound closure, as assessed using optical coherence tomography (OCT) imaging. Moreover, second harmonic generation (SHG) imaging revealed that seletinoid G recovered the reduced dermal collagen deposition seen in ultraviolet B (UVB)-irradiated human skin equivalents. Taken together, these results indicate that seletinoid G protects the skin barrier by accelerating wound healing in the epidermis and by repairing collagen deficiency in the dermis. Thus, seletinoid G could be a potent anti-aging agent for protecting the skin barrier. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Article
Altered Levels of Sphingosine, Sphinganine and Their Ceramides in Atopic Dermatitis Are Related to Skin Barrier Function, Disease Severity and Local Cytokine Milieu
Int. J. Mol. Sci. 2020, 21(6), 1958; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21061958 - 13 Mar 2020
Cited by 11 | Viewed by 1416
Abstract
Dysfunctional skin barrier plays a key role in the pathophysiology of atopic dermatitis (AD), a common inflammatory skin disease. Altered composition of ceramides is regarded as a major cause of skin barrier dysfunction, however it is not clear whether these changes are intrinsic [...] Read more.
Dysfunctional skin barrier plays a key role in the pathophysiology of atopic dermatitis (AD), a common inflammatory skin disease. Altered composition of ceramides is regarded as a major cause of skin barrier dysfunction, however it is not clear whether these changes are intrinsic or initiated by inflammation and aberrant immune response in AD. This study investigated the levels of free sphingoid bases (SBs) sphingosine and sphinganine and their ceramides and glucosylceramide in the stratum corneum (SC) and related them to skin barrier function, disease severity and local cytokine milieu. Ceramides were measured in healthy skin, and lesional and non-lesional skin of AD patients by a novel method based on deacylation of ceramides which were subsequently determined as corresponding sphingoid bases by using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The cytokine levels were determined by multiplex immunoassay. Atopic skin showed increased levels of most investigated markers, predominantly in lesional skin. The largest difference in respect to healthy skin was found for glucosylceramide with respective median values of 0.23 (IQR 0.18–0.61), 0.56 (IQR 0.32–0.76) and 19.32 (IQR 7.86–27.62) pmol/g protein for healthy, non-lesional and lesional skin. The levels of investigated ceramide markers were correlated with disease severity (scoring atopic dermatitis, SCORAD) and skin barrier function (trans-epidermal water loss, TEWL) and furthermore with cytokines involved in innate, Th-1, and Th-2 immune response. Interestingly, the strongest association with SCORAD was found for sphinganine/sphingosine ratio (r = −0.69, p < 0.001; non-lesional skin), emphasizing the importance of SBs in AD. The highest correlation with TEWL was found for glucosylceramide (r2 = 0.60, p < 0.001), which was investigated for the first time in AD. Findings that the changes in SBs and ceramide levels were predominant in lesional skin and their association with disease severity and cytokine levels suggest an immune-system driven effect. a novel analysis method demonstrates a robust and simple approach that might facilitate wider use of lipid biomarkers in the clinics e.g., to monitor (immune) therapy or dissect disease endotypes. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Review

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Review
The Role of MicroRNAs in Epidermal Barrier
Int. J. Mol. Sci. 2020, 21(16), 5781; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165781 - 12 Aug 2020
Cited by 2 | Viewed by 736
Abstract
MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier [...] Read more.
MicroRNAs (miRNAs), which mostly cause target gene silencing via transcriptional repression and degradation of target mRNAs, regulate a plethora of cellular activities, such as cell growth, differentiation, development, and apoptosis. In the case of skin keratinocytes, the role of miRNA in epidermal barrier integrity has been identified. Based on the impact of key genetic and environmental factors on the integrity and maintenance of skin barrier, the association of miRNAs within epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids is reviewed. The critical role of miRNAs in the epidermal barrier extends the use of miRNAs for control of relevant skin diseases such as atopic dermatitis, ichthyoses, and psoriasis via miRNA-based technologies. Most of the relevant miRNAs have been associated with keratinocyte differentiation and proliferation. Few studies have investigated the association of miRNAs with structural proteins of corneocytes and cornified envelopes, cell–cell adhesion, and skin lipids. Further studies investigating the association between regulatory and structural components of epidermal barrier and miRNAs are needed to elucidate the role of miRNAs in epidermal barrier integrity and their clinical implications. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Review
Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis
Int. J. Mol. Sci. 2020, 21(8), 2867; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082867 - 20 Apr 2020
Cited by 21 | Viewed by 2276
Abstract
Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously [...] Read more.
Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously assumed. Accumulating evidence from experimental, genetic, and clinical studies indicates that AD expression is a precondition for the later development of other atopic diseases, such as asthma, food allergies, and allergic rhinitis. Although the exact mechanisms of the disease pathogenesis remain unclear, it is evident that both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of AD pathology. This review explores recent findings on AD and the possible underlying mechanisms involved in its pathogenesis, which is characterized by dysregulation of immunological and skin barrier integrity and function, supporting the idea that AD is a systemic disease. These findings provide further insights for therapeutic developments aiming to repair the skin barrier and decrease inflammation. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Review
Anti-Aging Effects of GDF11 on Skin
Int. J. Mol. Sci. 2020, 21(7), 2598; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072598 - 09 Apr 2020
Cited by 6 | Viewed by 1784
Abstract
Human skin is composed of three layers: the epidermis, the dermis, and the hypodermis. The epidermis has four major cell layers made up of keratinocytes in varying stages of progressive differentiation. Skin aging is a multi-factorial process that affects every phase of its [...] Read more.
Human skin is composed of three layers: the epidermis, the dermis, and the hypodermis. The epidermis has four major cell layers made up of keratinocytes in varying stages of progressive differentiation. Skin aging is a multi-factorial process that affects every phase of its biology and function. The expression profiles of inflammation-related genes analyzed in resident immune cells demonstrated that these cells have a strong ability to regenerate adult skin stem cells and to produce endogenous substances such as growth differentiation factor 11 (GDF11). GDF11 appears to be the key to progenitor proliferation and/or differentiation. The preservation of youthful phenotypes has been tied to the presence of GDF11 in different human tissues, and, in the skin, this factor inhibits inflammatory responses. The protective role of GDF11 depends on a multi-factorial process implicating various types of skin cells such as keratinocytes, fibroblasts and inflammatory cells. GDF11 should be further studied for the purpose of developing novel therapies for the treatment of skin diseases. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Review
Loricrin: Past, Present, and Future
Int. J. Mol. Sci. 2020, 21(7), 2271; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072271 - 25 Mar 2020
Cited by 6 | Viewed by 3068
Abstract
The terminal differentiation of the epidermis is a complex physiological process. During the past few decades, medical genetics has shown that defects in the stratum corneum (SC) permeability barrier cause a myriad of pathological conditions, ranging from common dry skin to lethal ichthyoses. [...] Read more.
The terminal differentiation of the epidermis is a complex physiological process. During the past few decades, medical genetics has shown that defects in the stratum corneum (SC) permeability barrier cause a myriad of pathological conditions, ranging from common dry skin to lethal ichthyoses. Contrarily, molecular phylogenetics has revealed that amniotes have acquired a specialized form of cytoprotection cornification that provides mechanical resilience to the SC. This superior biochemical property, along with desiccation tolerance, is attributable to the proper formation of the macromolecular protein-lipid complex termed cornified cell envelopes (CE). Cornification largely depends on the peculiar biochemical and biophysical properties of loricrin, which is a major CE component. Despite its quantitative significance, loricrin knockout (LKO) mice have revealed it to be dispensable for the SC permeability barrier. Nevertheless, LKO mice have brought us valuable lessons. It is also becoming evident that absent loricrin affects skin homeostasis more profoundly in many more aspects than previously expected. Through an extensive review of aggregate evidence, we discuss herein the functional significance of the thiol-rich protein loricrin from a biochemical, genetic, pathological, metabolic, or immunological aspect with some theoretical and speculative perspectives. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Review
Molecular Mechanism of Epidermal Barrier Dysfunction as Primary Abnormalities
Int. J. Mol. Sci. 2020, 21(4), 1194; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041194 - 11 Feb 2020
Cited by 12 | Viewed by 1508
Abstract
Epidermal barrier integrity could be influenced by various factors involved in epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids. Dysfunction of this barrier can cause skin disorders, including eczema. Inversely, eczema can also damage the epidermal barrier. These interactions through vicious [...] Read more.
Epidermal barrier integrity could be influenced by various factors involved in epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids. Dysfunction of this barrier can cause skin disorders, including eczema. Inversely, eczema can also damage the epidermal barrier. These interactions through vicious cycles make the mechanism complicated in connection with other mechanisms, particularly immunologic responses. In this article, the molecular mechanisms concerning epidermal barrier abnormalities are reviewed in terms of the following categories: epidermal calcium gradients, filaggrin, cornified envelopes, desquamation, and skin lipids. Mechanisms linked to ichthyoses, atopic dermatitis without exacerbation or lesion, and early time of experimental irritation were included. On the other hand, the mechanism associated with epidermal barrier abnormalities resulting from preceding skin disorders was excluded. The molecular mechanism involved in epidermal barrier dysfunction has been mostly episodic. Some mechanisms have been identified in cultured cells or animal models. Nonetheless, research into the relationship between the causative molecules has been gradually increasing. Further evidence-based systematic data of target molecules and their interactions would probably be helpful for a better understanding of the molecular mechanism underlying the dysfunction of the epidermal barrier. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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Review
Trends in Atopic Dermatitis—From Standard Pharmacotherapy to Novel Drug Delivery Systems
Int. J. Mol. Sci. 2019, 20(22), 5659; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225659 - 12 Nov 2019
Cited by 14 | Viewed by 1533
Abstract
Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by robust burning and eczematous lacerations in diverse portions of the body. AD affects about 20% of both offspring and adults worldwide. The pathophysiology of AD combines environmental, hereditary, [...] Read more.
Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by robust burning and eczematous lacerations in diverse portions of the body. AD affects about 20% of both offspring and adults worldwide. The pathophysiology of AD combines environmental, hereditary, and immunological aspects, together with skin barrier dysfunction. The procedures used to prevent the disease are the everyday usage of creams to support the restoration of the epidermal barrier. The classical treatments include the use of topical corticosteroids as a first-line therapy, but also calcineurin inhibitors, antihistamines, antibiotics, phototherapy, and also immunosuppressant drugs in severe cases of AD. Topical drug delivery to deeper skin layers is a difficult task due to the skin anatomic barrier, which limits deeper penetration of drugs. Groundbreaking drug delivery systems, based on nanoparticles (NPs), have received much attention due to their ability to improve solubility, bioavailability, diffusion, targeting to specific types of cells, and limiting the secondary effects of the drugs employed in the treatment of AD. Even so, additional studies are still required to recognize the toxicological characteristics and long-term safety of NPs. This review discusses the current classical pharmacotherapy of AD against new nanoparticle skin delivery systems and their toxicologic risks. Full article
(This article belongs to the Special Issue Skin Epidermis and Barrier Function)
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