Decreased TET2/5-hmC reduces the integrity of the epidermal barrier via epigenetic dysregulation of filaggrin in psoriatic lesions.
J Dermatol Sci
; 113(3): 103-112, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38331641
ABSTRACT
BACKGROUND:
TET2 participates in tumor progression and intrinsic immune homeostasis via epigenetic regulation. TET2 has been reported to be involved in maintaining epithelial barrier homeostasis and inflammation. Abnormal epidermal barrier function and TET2 expression have been detected in psoriatic lesions. However, the mechanisms underlying the role of TET2 in psoriasis have not yet been elucidated.OBJECTIVE:
To define the role of TET2 in maintaining epithelial barrier homeostasis and the exact epigenetic mechanism in the dysfunction of the epidermal barrier in psoriasis.METHODS:
We analyzed human psoriatic skin lesions and datasets from the GEO database, and detected the expression of TET2/5-hmC together with barrier molecules by immunohistochemistry. We constructed epidermal-specific TET2 knockout mice to observe the effect of TET2 deficiency on epidermal barrier function via toluidine blue penetration assay. Further, we analyzed changes in the expression of epidermal barrier molecules by immunofluorescence in TET2-specific knockout mice and psoriatic model mice.RESULTS:
We found that decreased expression of TET2/5-hmC correlated with dysregulated barrier molecules in human psoriatic lesions. Epidermal-specific TET2 knockout mice showed elevated transdermal water loss associated with abnormal epidermal barrier molecules. Furthermore, we observed that TET2 knockdown in keratinocytes reduced filaggrin expression via filaggrin promoter methylation.CONCLUSION:
Aberrant epidermal TET2 affects the integrity of the epidermal barrier through the epigenetic dysregulation of epidermal barrier molecules, particularly filaggrin. Reduced TET2 expression is a critical factor contributing to an abnormal epidermal barrier in psoriasis.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Dioxigenases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Dermatol Sci
Assunto da revista:
DERMATOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China