The Whey Acidic Protein WFDC12 Is Specifically Expressed in Terminally Differentiated Keratinocytes and Regulates Epidermal Serine Protease Activity

Kalinina, Polina; Vorstandlechner, Vera; Buchberger, Maria; Eckhart, Leopold; Lengauer, Barbara; Golabi, Bahar; Laggner, Maria; Hiess, Manuela; Sterniczky, Barbara; Födinger, Dagmar; Petrova, Evgeniya; Elbe‐Bürger, Adelheid; Beer, Lucian; Hovnanian, Alain; Tschachler, Erwin; Mildner, Michael

doi:10.1016/j.jid.2020.09.025

Cited by 15 publications

(16 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…WFDC4 (also known as secretory leukocyte protease inhibitor, SLPI) strongly inhibits KLK7 [178]. A recent study describing the expression and function of WFDC12 (also known as whey acidic protein 2, WAP2) in human skin, reports WFDC12 as an upregulated protein in affected and nonaffected skin of NS patients and as a weak inhibitor of KLK7 [179]. WFDC14 (also known as peptidase inhibitor 3 or Elafin) is a weak inhibitor of KLK7 as well [178,180].…”

Section: Regulation Of Klk Activity In the Skin The Activitymentioning

confidence: 99%

Advances in understanding of Netherton syndrome and therapeutic implications

Petrova

Hovnanian

2020

Expert Opinion on Orphan Drugs

Self Cite

View full text Add to dashboard Cite

Introduction: Netherton syndrome (NS) is a rare and severe ichthyosis characterized by superficial scaling, skin inflammation, a specific hair shaft defect, severe atopic manifestations and multisystemic complications. It is an orphan disease with currently no satisfactory treatment. NS is caused by loss-offunction mutations in SPINK5 encoding the serine protease inhibitor LEKTI. NS patients present with ichthyosiform erythroderma or ichthyosis linearis circumflexa and show considerable clinical variability. Areas covered: Uncontrolled serine protease activity leads to a profound skin barrier defect and the release of pro-inflammatory and pro-allergic mediators by keratinocytes and immune cells. Improved understanding of NS pathogenesis has led to the successful use of repurposed biologics such as intravenous immunoglobulins and anti-IL-17A blockers. Between April 1, 2020 and November 18, 2020, authors searched for NS-relevant information in the following databases: MEDLINE, DrugBank, ClinicalTrials.gov, and patent datasets accessed through lens.org. Expert opinion: Specific KLK5 and/or KLK7 inhibitors represent the most promising disease-modifying treatments. They are currently being developed by several companies. Comprehension of the determinants of NS variability, flares and modification over time will be the foundation for precision medicine. While improved knowledge of the inflammatory and allergic pathways involved is still needed, clinical trials using repurposed biologics have already begun.

show abstract

Section: Regulation Of Klk Activity In the Skin The Activitymentioning

confidence: 99%

Advances in understanding of Netherton syndrome and therapeutic implications

Petrova

Hovnanian

2020

Expert Opinion on Orphan Drugs

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, the effect of whey proteins in improving the inflammatory status during wound healing in diabetic rats, in particular by reducing the expression of specific cytokines involved in the reparation, was previously reported [27]. Kalinina and collaborators [28] identified whey proteins, and in particular WFDC12, as a specific marker for the last stage of keratinocytes differentiation, probably enhancing the occurrence of epidermal homeostasis.…”

Section: Whey Valorization As Wound Repair Agentmentioning

confidence: 82%

Concentrated Buffalo Whey as Substrate for Probiotic Cultures and as Source of Bioactive Ingredients: A Local Circular Economy Approach towards Reuse of Wastewaters

et al. 2021

View full text Add to dashboard Cite

Waste reduction and reuse is a crucial target of current research efforts. In this respect, the present study was focused on providing an example of local investment in a simple process configuration that converts whey into value-added compounds and allows recovery of a clean water stream. In particular, buffalo milk whey obtained during mozzarella manufacturing was ultrafiltered in-house on spiral membrane modules (20 kDa), and the two obtained fractions, namely the retentate and the permeate, provided by the dairy factory, were further processed during this work. The use of an additional nanofiltration step allowed the recovery of high-quality water to be reused in the production cycle (machine rinsing water within the facility) and/or in agriculture, also reducing disposal costs and the environmental impact. The ultrafiltration retentate, on the other hand, was spray-dried and the powder obtained was used as the main substrate for the cultivation of Lactobacillus fermentum, a widely studied probiotic with anti-inflammatory, immunomodulatory and cholesterol-lowering properties. In addition, the same sample was tested in vitro on a human keratinocytes model. Resuspended concentrated whey powder improved cell reparation rate in scratch assays, assisted through time-lapse video-microscopy. Overall these data support the potential of buffalo whey as a source of biologically active components and recyclable water in the frame of a local circular economy approach.

show abstract

“…We have used scRNA-seq to characterize two types of keratinocyte differentiation, leading to the hard outer surface and the soft interscale epidermis of scutate scales. The methodology was adapted from successful scRNA-seq analyses of human and mouse skin 36 – 39 . scRNA-seq of mouse tail skin revealed two paths of keratinocyte differentiation into scale and interscale epidermis 40 .…”

Section: Discussionmentioning

confidence: 99%

“…Skin was excised from the leg of sacrificed animals and incubated in thermolysin (0.5 mg/ml) (Sigma-Aldrich) at 37 °C for 45 min. The lower dermis was removed using forceps and the remaining tissue, including the epidermis and parts of the upper dermis, was processed further according to protocols established for human skin 39 , 49 . For the isolation of cells, the tissue was split into two fractions that were incubated either in buffer-enzyme mix of the Whole Skin Dissociation Kit human (MACS Milteny Biotech) for 2.5 h at 37 °C or with 0.05% trypsin/EDTA (Thermo Fisher Scientific) and DNase 1 (10 µg/ml) (Roche Diagnostics) at 37 °C for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Single-cell transcriptomics defines keratinocyte differentiation in avian scutate scales

Lachner

Ehrlich

Wielscher

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

The growth of skin appendages, such as hair, feathers and scales, depends on terminal differentiation of epidermal keratinocytes. Here, we investigated keratinocyte differentiation in avian scutate scales. Cells were isolated from the skin on the legs of 1-day old chicks and subjected to single-cell transcriptomics. We identified two distinct populations of differentiated keratinocytes. The first population was characterized by mRNAs encoding cysteine-rich keratins and corneous beta-proteins (CBPs), also known as beta-keratins, of the scale type, indicating that these cells form hard scales. The second population of differentiated keratinocytes contained mRNAs encoding cysteine-poor keratins and keratinocyte-type CBPs, suggesting that these cells form the soft interscale epidermis. We raised an antibody against keratin 9-like cysteine-rich 2 (KRT9LC2), which is encoded by an mRNA enriched in the first keratinocyte population. Immunostaining confirmed expression of KRT9LC2 in the suprabasal epidermal layers of scutate scales but not in interscale epidermis. Keratinocyte differentiation in chicken leg skin resembled that in human skin with regard to the transcriptional upregulation of epidermal differentiation complex genes and genes involved in lipid metabolism and transport. In conclusion, this study defines gene expression programs that build scutate scales and interscale epidermis of birds and reveals evolutionarily conserved keratinocyte differentiation genes.

show abstract

The Whey Acidic Protein WFDC12 Is Specifically Expressed in Terminally Differentiated Keratinocytes and Regulates Epidermal Serine Protease Activity

Cited by 15 publications

References 60 publications

Advances in understanding of Netherton syndrome and therapeutic implications

Advances in understanding of Netherton syndrome and therapeutic implications

Concentrated Buffalo Whey as Substrate for Probiotic Cultures and as Source of Bioactive Ingredients: A Local Circular Economy Approach towards Reuse of Wastewaters

Single-cell transcriptomics defines keratinocyte differentiation in avian scutate scales

Contact Info

Product

Resources

About