Quantitative Proteomics Identifies Reduced NRF2 Activity and Mitochondrial Dysfunction in Atopic Dermatitis.
J Invest Dermatol
; 143(2): 220-231.e7, 2023 Feb.
Article
en En
| MEDLINE
| ID: mdl-36108803
ABSTRACT
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 RNAâmediated 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Dermatitis Atópica
Límite:
Humans
Idioma:
En
Revista:
J Invest Dermatol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Suiza