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Skin Diseases: Pathophysiological Mechanisms and Treatment Strategies

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 10313

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Prof. Dr. Daisuke Tsuruta

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Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan
Interests: autoimmune bullous disease; pemphigoid; hemidesmosome; focal adhesion; mast cell; hair biology; photodynamic therapy for infection

Special Issue Information

Dear Colleague

As the first physiological line of defense and the largest organ of the human body, skin always participates in the body’s functional activities and maintains the unity of opposites between the body and the natural environment. Skin plays a particularly important role in maintaining the health of the body. However, as abnormal conditions of the body can also be reflected on the surface of the skin, skin diseases are now attracting increasing attention. There are many reasons for skin diseases, such as skin diseases caused by infectious factors such as leprosy, scabies, mycosis, bacterial skin infection, and so on, which often have certain infectiousness.

At present, the treatment of dermatosis emphasizes more and more evidence-based medicine evidence. In this Special Issue, we are gathering manuscripts (reviews and articles) about the pathophysiological mechanisms for pemphigoid, hair loss, atopic dermatitis, and other skin diseases. A particular focus will be on the discovery of novel molecular mechanistic insights for a skin disease treatment, and discovery and test of novel targeted therapies.

Prof. Dr. Daisuke Tsuruta
Guest Editor

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Keywords

skin diseases
targeted therapies
molecular mechanism
pemphigoid
hair loss
skin cancer
infections
allergy

Published Papers (4 papers)

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Research

12 pages, 2762 KiB

Open AccessArticle

Preclinical Study of Immunological Isoxazole Derivatives as a Potential Support for Melanoma Chemotherapy

by Izabela Jęśkowiak, Benita Wiatrak, Adam Szeląg and Marcin Mączyński

Int. J. Mol. Sci. 2021, 22(20), 10920; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222010920 - 10 Oct 2021

Cited by 2 | Viewed by 1566

Abstract

(1) Background: Melanoma is an aggressive neoplasm derived from melanocyte precursors with a high metastatic potential. Responses to chemotherapy and immunotherapy for melanoma remain weak, underlining the urgent need to develop new therapeutic strategies for the treatment of melanoma. (2) Methods: The viability of NHDF and A375 cell cultures after the administration of the tested isoxazole derivatives was assessed after 24-h and 48-h incubation periods with the test compounds in the MTT test. ROS and NO scavenging analyses, a glycoprotein-P activity analysis, a migration assay, a test of apoptosis, and a multiple-criteria decision analysis were also performed. (3) Results: All compounds that were tested resulted in a slower migration of melanoma neoplastic cells. The mechanism of the antitumor activity of the tested compounds was confirmed—i.e., the pro-apoptotic activity of the compounds in A375 cell cultures. Compound O7K qualified for further research. (4) Conclusions: All the tested compounds inhibited the formation of melanoma metastases and demonstrated the ability to reduce the risk of developing drug resistance in the tumor. The MCDA results showed that O7K showed the strongest antitumor activity. Full article

(This article belongs to the Special Issue Skin Diseases: Pathophysiological Mechanisms and Treatment Strategies)

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12 pages, 12849 KiB

Open AccessArticle

GPNMB Extracellular Fragment Protects Melanocytes from Oxidative Stress by Inhibiting AKT Phosphorylation Independent of CD44

by Qianqian Wang, Yasutaka Kuroda, Lingli Yang, Sylvia Lai, Yukiko Mizutani, Arunasiri Iddamalgoda, Jiao Guo, Asako Yamamoto, Daiki Murase, Yoshito Takahashi, Leihong Xiang, Shintaro Inoue, Daisuke Tsuruta and Ichiro Katayama

Int. J. Mol. Sci. 2021, 22(19), 10843; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910843 - 07 Oct 2021

Cited by 4 | Viewed by 2623

Abstract

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that plays an important role in cancer metastasis and osteoblast differentiation. In the skin epidermis, GPNMB is mainly expressed in melanocytes and plays a critical role in melanosome formation. In our previous study, GPNMB was also found to be expressed in skin epidermal keratinocytes. In addition, decreased GPNMB expression was observed in the epidermis of lesional skin of patients with vitiligo. However, the exact role of keratinocyte-derived GPNMB and its effect on vitiligo is still unknown. In this study, we demonstrated that GPNMB expression was also decreased in rhododendrol-induced leukoderma, as seen in vitiligo. The extracellular soluble form of GPNMB (sGPNMB) was found to protect melanocytes from cytotoxicity and the impairment of melanogenesis induced by oxidative stress. Furthermore, the effect of rGPNMB was not altered by the knockdown of CD44, which is a well-known receptor of GPNMB, but accompanied by the suppressed phosphorylation of AKT but not ERK, p38, or JNK. In addition, we found that oxidative stress decreased both transcriptional GPNMB expression and sGPNMB protein expression in human keratinocytes. Our results suggest that GPNMB might provide novel insights into the mechanisms related to the pathogenesis of vitiligo and leukoderma. Full article

(This article belongs to the Special Issue Skin Diseases: Pathophysiological Mechanisms and Treatment Strategies)

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14 pages, 19972 KiB

Open AccessArticle

A Lower Irradiation Dose of 308 nm Monochromatic Excimer Light Might Be Sufficient for Vitiligo Treatment: A Novel Insight Gained from In Vitro and In Vivo Analyses

by Yasutaka Kuroda, Lingli Yang, Sylvia Lai, Jiao Guo, Tetsuya Sayo, Yoshito Takahashi, Daisuke Tsuruta and Ichiro Katayama

Int. J. Mol. Sci. 2021, 22(19), 10409; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910409 - 27 Sep 2021

Cited by 2 | Viewed by 2492

Abstract

A 308 nm monochromatic excimer light (MEL) is widely used to treat patients with vitiligo. However, dose optimization still needs to be clarified. This study aimed to obtain objective evidence regarding various doses of MEL irradiation, induced cell level changes in vitro, and skin level alterations in vivo. Cultured human keratinocytes were irradiated with MEL using various doses. After irradiation at low doses, stem cell factor, endothelin-1, and glycoprotein nonmetastatic melanoma protein B, factors that activate and protect melanocytes, were found to be significantly elevated in keratinocytes. After irradiation using medium and high doses, inflammatory cytokines were induced. The amount of ATP released and the level of inflammasome activation, which are known to be related to interleukin-1β activation, were also increased. The back skin of guinea pigs and mice were irradiated with MEL at varying doses. After irradiation, an increase of epidermal melanin and epidermal melanocytes was confirmed, using the minimal erythemal dose or less. In rhododendrol-induced leukoderma guinea pigs, a much lower dose of MEL irradiation was effective, when compared with the effective dose for control guinea pigs. Our results suggest that a lower irradiation dose of MEL might be sufficient and more suitable for repigmentation in vitiligo treatment. Full article

(This article belongs to the Special Issue Skin Diseases: Pathophysiological Mechanisms and Treatment Strategies)

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22 pages, 7903 KiB

Open AccessArticle

Anti-Inflammatory and Pro-Differentiating Properties of the Aryl Hydrocarbon Receptor Ligands NPD-0614-13 and NPD-0614-24: Potential Therapeutic Benefits in Psoriasis

by Giorgia Cardinali, Enrica Flori, Arianna Mastrofrancesco, Sarah Mosca, Monica Ottaviani, Maria Lucia Dell’Anna, Mauro Truglio, Antonella Vento, Marco Zaccarini, Christos C. Zouboulis and Mauro Picardo

Int. J. Mol. Sci. 2021, 22(14), 7501; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147501 - 13 Jul 2021

Cited by 9 | Viewed by 2527

Abstract

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor expressed in all skin cell types, plays a key role in physiological and pathological processes. Several studies have shown that this receptor is involved in the prevention of inflammatory skin diseases, e.g., psoriasis, atopic dermatitis, representing a potential therapeutic target. We tested the safety profile and the biological activity of NPD-0614-13 and NPD-0614-24, two new synthetic AhR ligands structurally related to the natural agonist FICZ, known to be effective in psoriasis. NPD-0614-13 and NPD-0614-24 did not alter per se the physiological functions of the different skin cell populations involved in the pathogenesis of inflammatory skin diseases. In human primary keratinocytes stimulated with tumor necrosis factor-α or lipopolysaccharide the compounds were able to counteract the altered proliferation and to dampen inflammatory signaling by reducing the activation of p38MAPK, c-Jun, NF-kBp65, and the release of cytokines. Furthermore, the molecules were tested for their beneficial effects in human epidermal and full-thickness reconstituted skin models of psoriasis. NPD-0614-13 and NPD-0614-24 recovered the psoriasis skin phenotype exerting pro-differentiating activity and reducing the expression of pro-inflammatory cytokines and antimicrobial peptides. These data provide a rationale for considering NPD-0614-13 and NPD-0614-24 in the management of psoriasis. Full article

(This article belongs to the Special Issue Skin Diseases: Pathophysiological Mechanisms and Treatment Strategies)

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