Cellular Mechanisms of Skin Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 29217

Special Issue Editor

Special Issue Information

Dear Colleagues,

Skin plays an important role in protecting and enhancing health. Because it interfaces with the environment, it has a prominent immunity role in protecting the body against pathogens. Although substantial research has been carried out to clarify the pathophysiology of skin diseases, much remains to be discovered regarding the cellular mechanisms of cutaneous disorders. In this context, the editors of Cells have set up an issue dedicated to cellular mechanisms of skin diseases. For this Special Issue, we invite research articles on various aspects of skin pathophysiology and cellular mechanisms of its diseases.

Dr. Mohamad Goldust
Guest Editor

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Published Papers (9 papers)

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Editorial

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2 pages, 182 KiB  
Editorial
Cellular Mechanisms of Skin Diseases
by Mohamad Goldust
Cells 2023, 12(6), 945; https://doi.org/10.3390/cells12060945 - 20 Mar 2023
Viewed by 1055
Abstract
Skin plays an important role in protecting and enhancing health [...] Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)

Research

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19 pages, 28034 KiB  
Article
Effect of Commonly Used Cosmetic Preservatives on Healthy Human Skin Cells
by Patrycja Głaz, Agata Rosińska, Sylwia Woźniak, Anna Boguszewska-Czubara, Anna Biernasiuk and Dariusz Matosiuk
Cells 2023, 12(7), 1076; https://doi.org/10.3390/cells12071076 - 3 Apr 2023
Cited by 6 | Viewed by 4457
Abstract
Cosmetic products contain preservatives to prevent microbial growth. The various types of preservatives present in skincare products applied on the skin induce many side effects. We tested several types of preservatives such as phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea (IU), the composition [...] Read more.
Cosmetic products contain preservatives to prevent microbial growth. The various types of preservatives present in skincare products applied on the skin induce many side effects. We tested several types of preservatives such as phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea (IU), the composition of gluconolactone and sodium benzoate (GSB), diazolidinyl urea (DU), and two grapefruit essential oils, one of which was industrially produced and a second which was freshly distilled from fresh grapefruit peels. This study aimed to find the relationship between preservative concentration, cell growth, collagen secretion, and cell viability. We hypothesized that these products induced a decrease in collagen secretion from human dermal fibroblasts. Our research, for the first time, addressed the overall effect of other preservatives on skin extracellular matrix (ECM) by studying their effect on metalloproteinase-2 (MMP-2) activity. Except for cytotoxicity and contact sensitivity tests, there are no studies of their effect on skin ECM in the available literature. These studies show potential antimicrobial activity, especially from the compounds IU and DU towards reference bacteria and the compounds methyl paraben and propyl paraben against reference fungi. The MTS test showed that fibroblasts are more sensitive to the tested group of preservatives than keratinocytes, which could be caused by the differences between the cells’ structures. The grapefruit oils exhibited the most cytotoxicity to both tested cell lines compared to all considered preservatives. The most destructive influence of preservatives on collagen synthesis was observed in the case of IU and DU. In this case, the homemade grapefruit oil turned out to be the mildest one. The results from a diverse group of preservatives show that whether they are natural or synthesized compounds, they require controlled use. Appropriate dosages and evaluation of preservative efficacy should not be the only aspects considered. The complex effect of preservatives on skin processes and cytotoxicity is an important topic for modern people. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)
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14 pages, 906 KiB  
Article
Enterotoxin Gene Cluster and selX Are Associated with Atopic Dermatitis Severity—A Cross-Sectional Molecular Study of Staphylococcus aureus Superantigens
by Leszek Blicharz, Maciej Żochowski, Ksenia Szymanek-Majchrzak, Joanna Czuwara, Mohamad Goldust, Krzysztof Skowroński, Grażyna Młynarczyk, Małgorzata Olszewska, Zbigniew Samochocki and Lidia Rudnicka
Cells 2022, 11(23), 3921; https://doi.org/10.3390/cells11233921 - 3 Dec 2022
Cited by 6 | Viewed by 1793
Abstract
Staphylococcus aureus superantigens (SAgs) have been reported to aggravate atopic dermatitis. However, comprehensive analyses of these molecules in multiple microniches are lacking. The present study involved 50 adult patients with active atopic dermatitis. S. aureus was isolated from the lesional skin, nonlesional skin, [...] Read more.
Staphylococcus aureus superantigens (SAgs) have been reported to aggravate atopic dermatitis. However, comprehensive analyses of these molecules in multiple microniches are lacking. The present study involved 50 adult patients with active atopic dermatitis. S. aureus was isolated from the lesional skin, nonlesional skin, and anterior nares. Multiplex-PCR was performed to identify genes encoding (1) selX (core genome); (2) seg, selI, selM, selN, selO, selU (enterotoxin gene cluster, EGC); and (3) sea, seb, sec, sed, see, tstH (classic SAgs encoded on other mobile genetic elements). The results were correlated to clinical parameters of the study group. selx and EGC were the most prevalent in all microniches. The number of SAg-encoding genes correlated between the anterior nares and nonlesional skin, and between the nonlesional and lesional skin. On lesional skin, the total number of SAg genes correlated with disease severity (total and objective SCORAD, intensity, erythema, edema/papulation, lichenification and dryness). Linear regression revealed that AD severity was predicted only by selx and EGC. This study revealed that selX and EGC are associated with atopic dermatitis severity. Anterior nares and nonlesional skin could be reservoirs of SAg-positive S. aureus. Restoring the physiological microbiome could reduce the SAg burden and alleviate syndromes of atopic dermatitis. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)
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14 pages, 1999 KiB  
Article
The Role of Hippo Signaling Pathway and ILK in the Pathophysiology of Human Hypertrophic Scars and Keloids: An Immunohistochemical Investigation
by Ilias G. Petrou, Sofia Nikou, Srinivas Madduri, Martha Nifora, Vasiliki Bravou and Daniel F. Kalbermatten
Cells 2022, 11(21), 3426; https://doi.org/10.3390/cells11213426 - 29 Oct 2022
Cited by 6 | Viewed by 2246
Abstract
Background: Keloids and hypertrophic scars are characterized by abnormal fibroblast activation and proliferation. While their molecular pathogenesis remains unclear, myofibroblasts have been associated with their development. Hippo pathway effectors YAP/TAZ promote cell proliferation and matrix stiffening. Integrin-linked kinase (ILK), a central component of [...] Read more.
Background: Keloids and hypertrophic scars are characterized by abnormal fibroblast activation and proliferation. While their molecular pathogenesis remains unclear, myofibroblasts have been associated with their development. Hippo pathway effectors YAP/TAZ promote cell proliferation and matrix stiffening. Integrin-linked kinase (ILK), a central component of focal adhesions that mediates cell–matrix interactions, has been linked to tissue repair and fibrosis. The aim of this study was to investigate the expression of key Hippo pathway molecules and ILK in hypertrophic scars and keloids. Methods: YAP/TAZ, TEAD4, ILK and a-SMA expression were evaluated by immunohistochemistry in keloids (n = 55), hypertrophic scars (n = 38) and normal skin (n = 14). Results: The expression of YAP/TAZ, TEAD4, ILK and a-SMA was higher in fibroblasts of keloids compared to hypertrophic scars while negative in normal skin. There was a significant positive correlation between the expression of ILK and Hippo pathway effectors. Conclusions: Our results suggest that the deregulation of Hippo signaling and ILK are implicated in keloid and hypertrophic scar formation. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)
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21 pages, 3667 KiB  
Article
Gene Profiling of a 3D Psoriatic Skin Model Enriched in T Cells: Downregulation of PTPRM Promotes Keratinocyte Proliferation through Excessive ERK1/2 Signaling
by Geneviève Rioux, Florence Turgeon, Gaëtan Le-Bel, Camille Grenier, Sylvain L. Guérin and Roxane Pouliot
Cells 2022, 11(18), 2904; https://doi.org/10.3390/cells11182904 - 16 Sep 2022
Cited by 3 | Viewed by 2555
Abstract
Psoriasis is a complex, immune-mediated skin disease involving a wide range of epithelial and immune cells. The underlying mechanisms that govern the epidermal defects and immunological dysfunction observed in this condition remain largely unknown. In recent years, the emergence of new, more sophisticated [...] Read more.
Psoriasis is a complex, immune-mediated skin disease involving a wide range of epithelial and immune cells. The underlying mechanisms that govern the epidermal defects and immunological dysfunction observed in this condition remain largely unknown. In recent years, the emergence of new, more sophisticated models has allowed the evolution of our knowledge of the pathogenesis of psoriasis. The development of psoriatic skin biomaterials that more closely mimic native psoriatic skin provides advanced preclinical models that will prove relevant in predicting clinical outcomes. In this study, we used a tissue-engineered, two-layered (dermis and epidermis) human skin substitute enriched in T cells as a biomaterial to study both the cellular and molecular mechanisms involved in psoriasis’ pathogenesis. Gene profiling on microarrays revealed significant changes in the profile of genes expressed by the psoriatic skin substitutes compared with the healthy ones. Two genes, namely, PTPRM and NELL2, whose products influence the ERK1/2 signaling pathway have been identified as being deregulated in psoriatic substitutes. Deregulation of these genes supports excessive activation of the ERK1/2 pathway in psoriatic skin substitutes. Most importantly, electrophoresis mobility shift assays provided evidence that the DNA-binding properties of two downstream nuclear targets of ERK1/2, both the NF-κB and Sp1 transcription factors, are increased under psoriatic conditions. Moreover, the results obtained with the inhibition of RSK, a downstream effector of ERK1/2, supported the therapeutic potential of inhibiting this signaling pathway for psoriasis treatment. In conclusion, this two-layered human psoriatic skin substitute enriched in T cells may prove particularly useful in deciphering the mechanistic details of psoriatic pathogenesis and provide a relevant biomaterial for the study of potential therapeutic targets. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)
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14 pages, 1902 KiB  
Article
Conditions That Simulate the Environment of Atopic Dermatitis Enhance Susceptibility of Human Keratinocytes to Vaccinia Virus
by Matthew G. Brewer, Stephanie R. Monticelli, Mary C. Moran, Benjamin L. Miller, Lisa A. Beck and Brian M. Ward
Cells 2022, 11(8), 1337; https://doi.org/10.3390/cells11081337 - 14 Apr 2022
Cited by 7 | Viewed by 2396
Abstract
Individuals with underlying chronic skin conditions, notably atopic dermatitis (AD), are disproportionately affected by infections from members of the herpesviridae, papovaviridae, and poxviridae families. Many patients with AD experience recurrent, widespread cutaneous viral infections that can lead to viremia, serious organ complications, and [...] Read more.
Individuals with underlying chronic skin conditions, notably atopic dermatitis (AD), are disproportionately affected by infections from members of the herpesviridae, papovaviridae, and poxviridae families. Many patients with AD experience recurrent, widespread cutaneous viral infections that can lead to viremia, serious organ complications, and even death. Little is known about how the type 2 inflammatory environment observed in the skin of AD patients impacts the susceptibility of epidermal cells (keratinocytes) to viral pathogens. Herein, we studied the susceptibility of keratinocytes to the prototypical poxvirus, vaccinia virus (VV)—the causative agent of eczema vaccinatum—under conditions that simulate the epidermal environment observed in AD. Treatment of keratinocytes with type 2 cytokines (IL-4 and -13) to simulate the inflammatory environment or a tight junction disrupting peptide to mirror the barrier disruption observed in AD patients, resulted in a differentiation-dependent increase in susceptibility to VV. Furthermore, pan JAK inhibition was able to diminish the VV susceptibility occurring in keratinocytes exposed to type 2 cytokines. We propose that in AD, the increased viral susceptibility of keratinocytes leads to enhanced virus production in the skin, which contributes to the rampant dissemination and pathology seen within patients. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)
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Review

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22 pages, 2933 KiB  
Review
An Updated Review of Hypertrophic Scarring
by Manjula P. Mony, Kelly A. Harmon, Ryan Hess, Amir H. Dorafshar and Sasha H. Shafikhani
Cells 2023, 12(5), 678; https://doi.org/10.3390/cells12050678 - 21 Feb 2023
Cited by 21 | Viewed by 4738
Abstract
Hypertrophic scarring (HTS) is an aberrant form of wound healing that is associated with excessive deposition of extracellular matrix and connective tissue at the site of injury. In this review article, we provide an overview of normal (acute) wound healing phases (hemostasis, inflammation, [...] Read more.
Hypertrophic scarring (HTS) is an aberrant form of wound healing that is associated with excessive deposition of extracellular matrix and connective tissue at the site of injury. In this review article, we provide an overview of normal (acute) wound healing phases (hemostasis, inflammation, proliferation, and remodeling). We next discuss the dysregulated and/or impaired mechanisms in wound healing phases that are associated with HTS development. We next discuss the animal models of HTS and their limitations, and review the current and emerging treatments of HTS. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)
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19 pages, 2819 KiB  
Review
Etiopathogenesis, Diagnosis, and Treatment Strategies for Lymphomatoid Papulosis with Particular Emphasis on the Role of the Immune System
by Danuta Nowicka, Paulina Mertowska, Sebastian Mertowski, Anna Hymos, Alicja Forma, Adam Michalski, Izabela Morawska, Rafał Hrynkiewicz, Paulina Niedźwiedzka-Rystwej and Ewelina Grywalska
Cells 2022, 11(22), 3697; https://doi.org/10.3390/cells11223697 - 21 Nov 2022
Cited by 6 | Viewed by 2826
Abstract
Lymphomatoid papulosis (LyP) is a very rare disease that belongs to the group of CD30+ lymphoproliferative skin diseases. LyP is localized or generalized and usually presents as isolated or clustered red/brown-red lesions in the form of nodules and/or papules. The course of the [...] Read more.
Lymphomatoid papulosis (LyP) is a very rare disease that belongs to the group of CD30+ lymphoproliferative skin diseases. LyP is localized or generalized and usually presents as isolated or clustered red/brown-red lesions in the form of nodules and/or papules. The course of the disease is in most cases mild; however, depending on concomitant risk factors and history, it may progress to lymphoma, significantly reducing the survival rate and prognosis. Importantly, the clinical picture of the disease remains somewhat ambiguous, leading to a large number of misdiagnoses that result in inappropriate treatment, which is usually insufficient to alleviate symptoms. In addition to clinical manifestations, the histological characteristics vary widely and usually overlap with other conditions, especially those belonging to the group of lymphoproliferative disorders. Although diagnosis remains a challenge, several recommendations and guidelines have been introduced to standardize and facilitate the diagnostic process. This article reviews the available literature on the most important aspects of etiopathogenesis, clinical and histopathological features, diagnostic criteria, and possible treatment strategies for LyP, with particular emphasis on the role of the immune system. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)
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14 pages, 585 KiB  
Review
The Role of Serum Th1, Th2, and Th17 Cytokines in Patients with Alopecia Areata: Clinical Implications
by Anna Waśkiel-Burnat, Marta Osińska, Anna Salińska, Leszek Blicharz, Mohamad Goldust, Małgorzata Olszewska and Lidia Rudnicka
Cells 2021, 10(12), 3397; https://doi.org/10.3390/cells10123397 - 2 Dec 2021
Cited by 43 | Viewed by 5371
Abstract
Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17E, IL-31 and IL-33) and Th17 (IL-17, IL-17F, IL-21, IL-22, IL-23 and TGF-β) cytokines was [...] Read more.
Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17E, IL-31 and IL-33) and Th17 (IL-17, IL-17F, IL-21, IL-22, IL-23 and TGF-β) cytokines was observed in patients with alopecia areata. Positive correlations between the severity of alopecia areata and an increased serum level of various cytokines including IL-2, TNF, IL-12, IL-17, and IL-17E were reported in the literature. An increased serum level of numerous cytokines, such as IL-2, IL-6, TNF, IL-12, IL-17E, and IL-22, was described as positively correlated with the duration of the disease. Moreover, it was shown that increased pre-treatment serum level of IL-12 was a positive, while increased serum levels of IL-4 and IL-13 were negative prognostic markers for the efficacy of diphenylcyclopropenone. In conclusion, alopecia areata is associated with the dysregulation of systemic Th1, Th2 and Th17 cytokines with their role in the pathogenesis, clinical manifestations and prognosis of the disease. Available data indicate the most significant role of serum IL-2, TNF, IL-12, IL-17, and IL-17E as markers of disease activity. The serum levels IL-4, IL-12 and IL-13 may be useful as potential predictors of diphenylcyclopropenone efficacy. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Skin Diseases)
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