TRPV4 Regulates the Development of Psoriasis by Controlling Adenosine Triphosphate Expression in Keratinocytes and the Neuroimmune System.
J Invest Dermatol
; 143(12): 2356-2365.e5, 2023 12.
Article
em En
| MEDLINE
| ID: mdl-37263487
ABSTRACT
TRPV4 is a calcium ion channel that is widely expressed in various cells. It is also involved in physiological and pathological processes. However, the role of TRPV4 in psoriasis remains unknown. We aimed to investigate the role of TRPV4 in psoriasis using human psoriasis skin samples and an imiquimod-induced psoriasis-like mouse model. Keratinocytes in human psoriasis skin had high TRPV4 expression. Trpv4-knockout mice had less severe dermatitis than wild-type mice in the imiquimod-induced mouse model. Knockout mice had significantly reduced epidermal thickness and a low number of infiltrated CD3+ T cells and CD68+ macrophages on the basis of histopathological studies and decreased mRNA expression of Il17a, Il17f, and Il23, as detected through qPCR. Furthermore, knockout mice had a significantly low expression of neuropeptides and the neuron marker PGP9.5. Adenosine triphosphate release was significantly suppressed by TRPV4 knockdown in both human and mouse keratinocytes in vitro. Finally, treatment with TRPV4 antagonist was significantly effective in preventing the progression of psoriasis-like dermatitis. In conclusion, TRPV4 mediates the expression of keratinocyte-derived adenosine triphosphate and increases the secretion of neuropeptides, resulting in the activation and amplification of IL-23/Th17 responses. Hence, TRPV4 can serve as a novel therapeutic target in psoriasis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Neuropeptídeos
/
Dermatite
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Invest Dermatol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão