Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis

Nomura, Hayato; Suganuma, Mutsumi; Takeichi, Takuya; Kono, Michihiro; Isokane, Yuki; Sunagawa, Ko; Kobashi, Mina; Sugihara, Satoru; Kajita, Ai; Miyake, Tomoko; Hirai, Yoji; Akiyama, Masashi; Morizane, Shin

doi:10.3390/ijms21030913

Cited by 17 publications

(15 citation statements)

References 34 publications

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“…Moreover, the increased protease activity in AD leads to permeability barrier dysfunction, inflammation, and defects in the antimicrobial barrier. Due to the proteolytic effects, external antigens of AD can easily invade the epidermis, resulting in dermatitis, coupled with the induction of Th2 cytokines [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

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Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis

Valenzuela

Fernández²,

Aroca

et al. 2020

Biomolecules

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Atopic dermatitis (AD) is a protease-modulated chronic disorder with heterogenous clinical manifestations which may lead to an imprecise diagnosis. To date, there are no diagnostic protease tests for AD. We explored the gingival crevicular fluid (GCF) protease profile of individuals with moderate/severe AD compared to healthy controls. An exploratory case-control study was conducted. AD patients (n = 23) and controls (n = 21) were enrolled at the International Center for Clinical Studies, Santiago, Chile. Complete dermatological and periodontal evaluations (involving the collection of GCF samples) were made. The levels of 35 proteases were analyzed using a human protease antibody array in matching AD patients (n = 6) and controls (n = 6) with healthy periodontium. The GCF levels of zinc-binding ADAM8, ADAM9, MMP8, Neprilysin/CD10, aspartyl-binding Cathepsin E, serin-binding Protein convertase9, and uPA/Urokinase proteases were lower in moderate/severe AD patients compared to controls (p < 0.05). No inter-group differences in the levels of the other 28 proteases were found. MMP8, Cathepsin E, and ADAM9 were the biomarkers with the highest sensitivity and specificity regarding the detection of AD (p < 0.05). The area under receiver operating characteristic (ROC) curve for MMP8 was 0.83 and MMP8 + ADAMP9 was 0.90, with no significant differences (p = 0.132). A combined model of MMP8, Cathepsin E, and ADAM9 was not considered since it did not converge. Then, levels of MMP8 in GCF were determined using a multiplex bead immunoassay in 23 subjects with AD and 21 healthy subjects. Lower levels of MMP8 in the GCF from the AD group versus healthy group (p = 0.029) were found. This difference remained significant after adjustment by periodontitis (p = 0.042). MMP8 revealed the diagnostic potential to identify AD patients versus healthy controls, (ROC area = 0.672, p < 0.05). In conclusion, differences in the protease profile between AD and control patients were associated with MMP8, Cathepsin E, and ADAM9. Based on the multiplex assay results, MMP8 was lower in AD patients than controls, suggesting that MMP8 may be a diagnostic biomarker candidate.

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Section: Introductionmentioning

confidence: 99%

“…The use of biomarkers may help in better defining the clinical heterogeneity of the disease and contribute to its treatment. Currently, there are no biomarkers that can differentiate the disease from other entities or indicate the clinical status of AD in adults [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis

Valenzuela

Fernández²,

Aroca

et al. 2020

Biomolecules

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“…This is an example of how the study of a rare syndrome, NS, reveals pathways that can be therapeutically exploited for the treatment of common skin disorders. Very recently, analysis of a relatively large cohort of AD patients found increased trypsin‐ and chymotrypsin‐like activities both at lesional and at non‐lesional sites of their epidermis 113 . These findings further support the development of new KLK5 inhibitors as new cosmeceuticals and/or pharmaceuticals.…”

Section: Targeting Epidermal Proteolysis: From Treatment Of Ichthyoses To Innovative Cosmeceuticalsmentioning

confidence: 69%

Redirecting drug repositioning to discover innovative cosmeceuticals

Sotiropoulou

Zingkou

Pampalakis

2021

Experimental Dermatology

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Skin appearance is essential for self‐esteem and quality of life; consequently, skin care products represent a huge market. In particular, cosmeceuticals constitute a hybrid category of skin care formulations, at the interphase of cosmetics and pharmaceuticals, rationally designed to target (patho) physiological mechanisms aiming to enhance skin health and appearance. Cosmeceuticals are marketed as anti‐ageing, anti‐wrinkle, hair regrowth, skin whitening and wound healing agents with special emphasis on scar‐free healing. An overview on recent cutting‐edge advances concerning the discovery and development of enhanced performance cosmeceuticals by drug repositioning approaches is presented here. In this context, we propose “target repositioning,” a new term, to highlight that druggable protein targets implicated in multiple diseases (hubs in the diseasome) can be exploited to accelerate the discovery of molecularly targeted cosmeceuticals that can promote skin health as an added benefit, which is a novel concept not described before. In this direction, emphasis is placed on the role of mouse models, for often untreatable skin diseases, as well as recent breakthroughs on monogenic rare skin syndromes, in promoting compound repositioning to innovative cosmeceuticals.

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“…Among the four receptors, the functional roles of PAR2 have been more clearly described in AD [38]. Protease activity and PAR2 expression in keratinocytes and PAR+ peripheral nerves were prominently increased in lesioned skin of AD patients [41,42]. PAR2 can be activated by specific serine and cysteine proteases such as tryptase, kallikreins (KLK), and cathepsin.…”

Section: Protease and Protease-activated Receptors (Pars)mentioning

confidence: 99%

The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

Wong

Yen

Lee

2021

IJMS

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Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

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Multifaceted Analyses of Epidermal Serine Protease Activity in Patients with Atopic Dermatitis

Cited by 17 publications

References 34 publications

Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis

Gingival Crevicular Fluid Zinc- and Aspartyl-Binding Protease Profile of Individuals with Moderate/Severe Atopic Dermatitis

Redirecting drug repositioning to discover innovative cosmeceuticals

The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

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