Proteomics

Dataset Information

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Atopic dermatitis epidermis PCT-DIA


ABSTRACT: Atopic Dermatitis (AD) is the most common inflammatory skin disease and characterized by a deficient epidermal barrier and cutaneous inflammation. Genetic studies suggest a key role of keratinocytes in AD pathogenesis, but the alterations in the proteome that occur in the entire epidermis have not been defined. Employing a pressure-cycling technology-data-independent acquisition (PCT-DIA) approach, we performed quantitative proteomics of epidermis from healthy volunteers and lesional and non-lesional skin of AD patients. Results were validated by targeted proteomics using parallel reaction monitoring mass spectrometry or by immunofluorescence staining. The identified proteins reflect the strong inflammation in lesional skin and the defect in keratinocyte differentiation and epidermal stratification. Most importantly, they reveal impaired activation of the NRF2-antioxidant pathway and reduced abundance of mitochondrial proteins involved in key metabolic pathways in the epidermis. These results provide insight into the molecular alterations in the epidermis of AD patients and identify novel targets for pharmaceutical intervention.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Skin

DISEASE(S): Atopic Dermatitis

SUBMITTER: Ulrich auf dem Keller  

LAB HEAD: Ulrich auf dem Keller

PROVIDER: PXD025431 | Pride | 2022-10-04

REPOSITORIES: Pride

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Publications

Quantitative Proteomics Identifies Reduced NRF2 Activity and Mitochondrial Dysfunction in Atopic Dermatitis.

Koch Michael M   Kockmann Tobias T   Rodriguez Elke E   Wehkamp Ulrike U   Hiebert Paul P   Ben-Yehuda Greenwald Maya M   Stölzl Dora D   Beer Hans-Dietmar HD   Tschachler Erwin E   Weidinger Stephan S   Werner Sabine S   Auf dem Keller Ulrich U  

The Journal of investigative dermatology 20220913 2


Atopic dermatitis is the most common inflammatory skin disease and is characterized by a deficient epidermal barrier and cutaneous inflammation. Genetic studies suggest a key role of keratinocytes in atopic dermatitis pathogenesis, but the alterations in the proteome that occur in the full epidermis have not been defined. Using a pressure-cycling technology and data-independent acquisition approach, we performed quantitative proteomics of epidermis from healthy volunteers and lesional and nonles  ...[more]

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