The hand eczema proteome: imbalance of epidermal barrier proteins

Molin, Sonja; Merl, Juliane; Dietrich, Kai; Regauer, M.; Flaig, Michael J.; Letulé, Valerie; Saucke, T.; Herzinger, Thomas; Ruzicka, Thomas; Hauck, Stefanie M.

doi:10.1111/bjd.13418

Cited by 51 publications

(53 citation statements)

References 36 publications

(64 reference statements)

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“…Nevertheless, studying the hand eczema proteome, Molin et al . observed some similar changes to those reported here, that is increased SPRR2B, but also observed the opposite for other proteins, for example, reduced kallikrein 5 and increased S100A7‐9 and 11. Like our study, decreased levels of suprabasin were also observed in subjects with dandruff.…”

Section: Discussionsupporting

confidence: 88%

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

Voegeli

Monneuse²,

Schoop

et al. 2017

Intern J of Cosmetic Sci

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BACKGROUND:The effect of photodamage on facial stratum corneum (SC) is still poorly understood. OBJECTIVE: To describe the SC proteome from tape strippings of Caucasian SC from photoexposed cheek and photoprotected postauricular (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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 crosstalk 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.R esum e CONTEXTE: Les effets des dommages dus a l'exposition a la lumiere sur le stratum corneum (SC) sont encore mal compris. OBJECTIFS: D ecrire le prot eome du SC issu de pr el evements par bandes adh esives provenant de la joue, expos ee a la lumi ere, et de la r egion post-auriculaire, prot eg ee de la lumi ere, de sujets caucasiens.A cette fin, une analyse globale des dommages cutan es dus a l'exposition a la lumi er...

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Section: Discussionsupporting

confidence: 88%

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

Voegeli

Monneuse²,

Schoop

et al. 2017

Intern J of Cosmetic Sci

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“…Each approximately 0.5-mg sample was measured on an LTQ OrbitrapXL (Thermo Fisher Scientific) coupled to an Ultimate3000 nano-RSLC device (Dionex) as described previously (Hauck et al, 2010;Molin et al, 2015).…”

Section: Lc-ms/ms Measurement Label-free Quantitative Analysis and mentioning

confidence: 99%

Comparative Proteomics Analysis of Arabidopsis Phloem Exudates Collected During the Induction of Systemic Acquired Resistance

et al. 2016

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ORCID IDs: 0000-0002-5467-7290 (P.C.); 0000-0002-3422-4083 (J.M.-P.).Systemic acquired resistance (SAR) is a plant defense response that provides long-lasting, broad-spectrum pathogen resistance to uninfected systemic leaves following an initial localized infection. In Arabidopsis (Arabidopsis thaliana), local infection with virulent or avirulent strains of Pseudomonas syringae pv tomato generates long-distance SAR signals that travel from locally infected to distant leaves through the phloem to establish SAR. In this study, a proteomics approach was used to identify proteins that accumulate in phloem exudates in response to the induction of SAR. To accomplish this, phloem exudates collected from mock-inoculated or SAR-induced leaves of wild-type Columbia-0 plants were subjected to label-free quantitative liquid chromatography-tandem mass spectrometry proteomics. Comparing mock-and SAR-induced phloem exudate proteomes, 16 proteins were enriched in phloem exudates collected from SAR-induced plants, while 46 proteins were suppressed. SAR-related proteins THIOREDOXIN h3, ACYL-COENZYME A-BINDING PROTEIN6, and PATHOGENESIS-RELATED1 were enriched in phloem exudates of SAR-induced plants, demonstrating the strength of this approach and suggesting a role for these proteins in the phloem during SAR. To identify novel components of SAR, transfer DNA mutants of differentially abundant phloem proteins were assayed for SAR competence. This analysis identified a number of new proteins (m-type thioredoxins, major latex protein-like protein, ULTRAVIOLET-B RESISTANCE8 photoreceptor) that contribute to the SAR response. The Arabidopsis SAR phloem proteome is a valuable resource for understanding SAR long-distance signaling and the dynamic nature of the phloem during plant-pathogen interactions.

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“…Recent studies have suggested that cumulative exposure to irritants impairs skin barrier integrity, and that an inherited skin barrier impairment due to FLG mutations appears to increase allergen penetration . In addition, skin barrier dysfunction has recently been shown to play an essential role in the pathogenesis of chronic hand eczema, for example by downregulation of barrier genes including FLG , FLG2 and hornerin . However, the interplay between hand eczema and endogenous factors such as AD and FLG mutations, as well as exogenous factors including exposure to contact allergens and irritants, is not completely understood.…”

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confidence: 99%

Predictive factors of self-reported hand eczema in adult Danes: a population-based cohort study with 5-year follow-up

et al. 2016

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SummaryBackground Information about predictive factors of hand eczema is crucial for primary prevention. Objectives To investigate predictive factors of hand eczema in adult Danes from the general population. Methods Participants from a cross-sectional 5-year follow-up study in the general population, aged 18-72 years (n = 2270), completed questionnaires about skin health and were grouped into four hand eczema groups: 'never', 'incident', 'nonpersistent' and 'persistent'. Multiple logistic regression models adjusted for age group and sex were used to evaluate associations with baseline variables. The participation rate for the follow-up study was 66Á5% (29Á7% of the participants originally invited to the baseline study). Results A history of atopic dermatitis (AD) was associated with both persistent and incident hand eczema [odds ratio (OR) 9Á0, 95% confidence interval (95% CI) 5Á6-14Á4 and OR 3Á0, 95% CI 1Á7-5Á2, respectively]. Thus, even in adulthood, a history of AD should be considered as a predictor of incident hand eczema. While filaggrin gene (FLG) null mutations were not associated with incident hand eczema, a statistically significant association was observed with persistent hand eczema (OR 3Á1, 95% CI 1Á8-5Á2). Finally, contact sensitization (23 allergens without nickel) was also associated with persistent hand eczema (OR 2Á5, 95% CI 1Á2-5Á0), independently of a history of AD. Conclusions This study confirms a history of AD as the strongest predictor of persistent hand eczema. We additionally found that a history of AD was associated with incident hand eczema in adults, in contrast to FLG mutations, which were associated only with persistent hand eczema in individuals with a history of AD, and not with incident hand eczema. Our study adds new knowledge to the interplay between AD, FLG mutations and hand eczema in the adult general population.

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The hand eczema proteome: imbalance of epidermal barrier proteins

Abstract: Our results corroborate the assumption that skin barrier dysfunction plays an essential role in the pathogenesis of CHE.

Cited by 51 publications

References 36 publications

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

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

Comparative Proteomics Analysis of Arabidopsis Phloem Exudates Collected During the Induction of Systemic Acquired Resistance

Predictive factors of self-reported hand eczema in adult Danes: a population-based cohort study with 5-year follow-up

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