Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype

Trzeciak, Magdalena; Sakowicz-Burkiewicz, Monika; Wesserling, Martyna; Dobaczewska, Daria; Gleń, Jolanta; Nowicki, Roman; Pawełczyk, Tadeusz

doi:10.2340/00015555-2482

Cited by 34 publications

(38 citation statements)

References 29 publications

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“…Rinnerthaler et al [32] reported some similar changes with intrinsic ageing to those that we found in our cheek samples: decreased loricrin and SPRR 1A, 2E, S100A7, A8 and A9 levels. However, unlike the study of Trzeciak et al [33], we observed decreased levels of SPRR1A compared with their recorded increases in subjects with atopic dermatitis. Nevertheless, studying the hand eczema proteome, Molin et al [16] 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.…”

Section: Discussioncontrasting

confidence: 99%

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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: Discussioncontrasting

confidence: 99%

“…However, unlike the study of Trzeciak et al . , we observed decreased levels of SPRR1A compared with their recorded increases in subjects with atopic dermatitis. Nevertheless, studying the hand eczema proteome, Molin et al .…”

Section: Discussionmentioning

confidence: 41%

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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“…These findings provide evidence of the involvement of SERPINB3/SERPINB4 in skin inflammation. SPRR3 is a cornified envelope (CE) precursor protein that is virtually undetectable in normal skin . During the late stages of epidermal differentiation, the formation of the CE is essential for epidermal barrier function and involves the replacement of the plasma membrane by cross‐linkage of precursor proteins such as involucrin, SPRRs and loricrin.…”

Section: Discussionmentioning

confidence: 99%

Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa

Zouboulis

Costa

Makrantonaki

et al. 2020

Acad Dermatol Venereol

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Background The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease‐driving mechanisms and tissue targeting. Objective Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. Methods Hidradenitis suppurativa/acne inversa molecular taxonomy and key signalling pathways were studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non‐lesional skin obtained from female HS patients and matched healthy controls using the Agilent array platform. The differential gene expression was confirmed by quantitative real‐time PCR and targeted protein characterization via immunohistochemistry in another set of female patients. HS‐involved skin compartments were also recognized by immunohistochemistry. Results Alterations to key regulatory pathways involving glucocorticoid receptor, atherosclerosis, HIF1α and IL17A signalling as well as inhibition of matrix metalloproteases were detected. From a functional standpoint, cellular assembly, maintenance and movement, haematological system development and function, immune cell trafficking and antimicrobial response were key processes probably being affected in HS. Sixteen genes were found to characterize HS from a molecular standpoint (DEFB4, MMP1, GJB2, PI3, KRT16, MMP9, SERPINB4, SERPINB3, SPRR3, S100A8, S100A9, S100A12, S100A7A (15), KRT6A, TCN1, TMPRSS11D). Among the proteins strongly expressed in HS, calgranulin‐A, calgranulin‐B and serpin‐B4 were detected in the hair root sheath, koebnerisin and connexin‐32 in stratum granulosum, transcobalamin‐1 in stratum spinosum/hair root sheath, small prolin‐rich protein‐3 in apocrine sweat gland ducts/sebaceous glands‐ducts and matrix metallopeptidase‐9 in resident monocytes. Conclusion Our findings highlight a panel of immune‐related drivers in HS, which influence innate immunity and cell differentiation in follicular and epidermal keratinocytes as well as skin glands.

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“…The A-repeat shares homology with hornerin, whereas the B-repeat is reminiscent of filaggrin (Wu et al, 2009). Filaggrin 2 has been suggested to play a role in the maintenance of the epidermal barrier given its partial similarity to filaggrin (Wu et al, 2009), given the facts that its expression is affected in atopic dermatitis (Trzeciak et al, 2017) and it is rich in histidine and glutamine residues (Wu et al, 2009), sources of the natural moisturizing factors urocanic acid and pyrrolidone carboxylic acid, respectively (Hon et al, 2013). In addition, polymorphisms in the FLG2 gene have been found to be associated with the propensity to develop atopic dermatitis (Margolis et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A

Mohamad

Sarig

Godsel

et al. 2018

Journal of Investigative Dermatology

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Peeling skin syndromes form a large and heterogeneous group of inherited disorders characterized by superficial detachment of the epidermal cornified cell layers, often associated with inflammatory features. Here we report on a consanguineous family featuring noninflammatory peeling of the skin exacerbated by exposure to heat and mechanical stress. Whole exome sequencing revealed a homozygous nonsense mutation in FLG2, encoding filaggrin 2, which cosegregated with the disease phenotype in the family. The mutation was found to result in decreased FLG2 RNA levels as well as almost total absence of filaggrin 2 in the patient epidermis. Filaggrin 2 was found to be expressed throughout the cornified cell layers and to colocalize with corneodesmosin that plays a crucial role in maintaining cell-cell adhesion in this region of the epidermis. The absence of filaggrin 2 in the patient skin was associated with markedly decreased corneodesmosin expression, which may contribute to the peeling phenotype displayed by the patients. Accordingly, using the dispase dissociation assay, we showed that FLG2 downregulation interferes with keratinocyte cell-cell adhesion. Of particular interest, this effect was aggravated by temperature elevation, consistent with the clinical phenotype. Restoration of corneodesmosin levels by ectopic expression rescued cell-cell adhesion. Taken together, the present data suggest that filaggrin 2 is essential for normal cell-cell adhesion in the cornified cell layers.

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Expression of Cornified Envelope Proteins in Skin and Its Relationship with Atopic Dermatitis Phenotype

Cited by 34 publications

References 29 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

Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa

Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A

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