LncRNA-WAKMAR2 regulates expression of CLDN1 to affect skin barrier through recruiting c-Fos.
Contact Dermatitis
; 88(3): 188-200, 2023 Mar.
Article
em En
| MEDLINE
| ID: mdl-36461623
ABSTRACT
BACKGROUND:
Chronic actinic dermatitis (CAD) is an immune-mediated photo-allergic skin disease. In the clinic, the treatment of this disease is hampered by the lack of proper understanding of the skin barrier dysfunction mechanism.OBJECTIVE:
To illuminate the mechanism of skin barrier dysfunction in CAD.METHODS:
Transcriptome sequencing and protein profiling were used to detect skin barrier injury-related genes. RNA pull down, a promoter-reporter gene assay, and chromatin isolation by RNA purification-sequencing were used to elucidate the effect of WAKMAR2 in skin barrier functionality.RESULTS:
Transcriptome sequencing from patient's tissues showed a significantly decreased expression of WAKMAR2. Down-regulation of WAKMAR2 destroyed the keratinocyte barrier. Moreover, WAKMAR2 can directly bind to the c-Fos protein. This novel long non-coding RNA (LncRNA)-protein complexes were targeted to the CLDN1 promotor. Overexpression of WAKMAR2 enhanced the promoter activity of CLDN1, while the addition of AP-1 inhibitor could reverse this phenomenon. Furthermore, our in vivo results suggested that expression of WAKMAR2 was required for the repair of skin damage in mice induced by ultraviolet irradiation.CONCLUSIONS:
We identified a crucial LncRNA (WAKMAR2) for the protection of the skin barrier in vitro and in vivo. Mechanically, it can specifically interact with c-Fos protein for the regulation of CLDN1, a finding which could be applied for CAD treatment.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Dermatite Alérgica de Contato
/
Dermatite Atópica
/
RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article