Quantitative proteomics identifies reduced NRF2 activity and mitochondrial dysfunction in Atopic Dermatitis
| Autor: | Michael Koch, Tobias Kockmann, Elke Rodriguez, Ulrike Wehkamp, Paul Hiebert, Maya Ben-Yehuda Greenwald, Dora Stölzl, Hans-Dietmar Beer, Erwin Tschachler, Stephan Weidinger, Sabine Werner, Ulrich Auf dem Keller |
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| Přispěvatelé: | University of Zurich |
| Jazyk: | angličtina |
| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Koch, M, Kockmann, T, Rodriguez, E, Wehkamp, U, Hiebert, P, Ben-Yehuda Greenwald, M, Stölzl, D, Beer, H-D, Tschachler, E, Weidinger, S, Werner, S & auf dem Keller, U 2023, ' Quantitative proteomics identifies reduced NRF2 activity and mitochondrial dysfunction in Atopic Dermatitis ', Journal of Investigative Dermatology, vol. 143, no. 2, pp. 220-237.e7 . https://doi.org/10.1016/j.jid.2022.08.048 Journal of Investigative Dermatology, 143 (2) |
| ISSN: | 0022-202X 1523-1747 |
| DOI: | 10.1016/j.jid.2022.08.048 |
| Popis: | 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 nonlesional patient skin. Results were validated by targeted proteomics using parallel reaction monitoring mass spectrometry and immunofluorescence staining. Proteins that were differentially abundant in the epidermis of patients with atopic dermatitis versus in healthy control reflect the strong inflammation in lesional skin and the defect in keratinocyte differentiation and epidermal stratification that already characterizes nonlesional skin. Most importantly, they reveal impaired activation of the NRF2-antioxidant pathway and reduced abundance of mitochondrial proteins involved in key metabolic pathways in the affected epidermis. Analysis of primary human keratinocytes with small interfering RNA‒mediated NRF2 knockdown revealed that the impaired NRF2 activation and mitochondrial abnormalities are partially interlinked. These results provide insight into the molecular alterations in the epidermis of patients with atopic dermatitis and identify potential targets for pharmaceutical intervention. Journal of Investigative Dermatology, 143 (2) ISSN:0022-202X ISSN:1523-1747 |
| Databáze: | OpenAIRE |
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