Keratin 5-Cre-driven deletion of Ncstn in an acne inversa-like mouse model leads to a markedly increased IL-36a and Sprr2 expression.
Front Med
; 14(3): 305-317, 2020 Jun.
Article
en En
| MEDLINE
| ID: mdl-31884525
ABSTRACT
Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in γ-secretase component genes. We and other researchers showed that nicastrin (NCSTN) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific Ncstn conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In Ncstnflox/flox;K5-Cre mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF-α, IL-23A, IL-1ß, and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the Ncstnflox/flox;K5-Cre mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other Sprr2 genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and involved in the malfunction of the skin barrier in the pathogenesis of AI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
/
Interleucina-1
/
Hidradenitis Supurativa
/
Queratina-5
/
Secretasas de la Proteína Precursora del Amiloide
/
Proteínas Ricas en Prolina del Estrato Córneo
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Front Med
Año:
2020
Tipo del documento:
Article
País de afiliación:
China