Lysine-specific demethylase 1 as a corepressor of mineralocorticoid receptor.
Hypertens Res
; 45(4): 641-649, 2022 Apr.
Article
en En
| MEDLINE
| ID: mdl-35177789
ABSTRACT
Mineralocorticoid receptor (MR) and its ligand aldosterone play a central role in controlling blood pressure by promoting sodium reabsorption in the kidney. Coregulators are recruited to regulate the activation of steroid hormone receptors. In our previous study, we identified several new candidates for MR coregulators through liquid chromatography-tandem mass spectrometry analysis using a biochemical approach. Lysine-specific demethylase 1 (LSD1) was identified as a candidate. The relationship between LSD1 and salt-sensitive hypertension has been reported; however, the role of MR in this condition is largely unknown. Here, we investigated the functions of LSD1 as a coregulator of MR. First, a coimmunoprecipitation assay using HEK293F cells showed specific interactions between MR and LSD1. A chromatin immunoprecipitation study demonstrated LSD1 recruitment to the gene promoter of epithelial Na+ channel (ENaC), a target gene of MR. Reduced LSD1 expression by treatment with shRNA potentiated the hormonal activation of ENaC and serum/glucocorticoid-regulated kinase 1, another target gene of MR, indicating that LSD1 is a corepressor of MR. In an animal study, mice with kidney-specific LSD1 knockout (LSD1flox/floxKSP-Cre mice) developed hypertension after a high-salt diet without elevation of aldosterone levels, which was counteracted by cotreatment with spironolactone, an MR antagonist. In conclusion, our in vitro and in vivo studies demonstrated that LSD1 is a newly identified corepressor of MR.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores de Mineralocorticoides
/
Hipertensión
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Hypertens Res
Asunto de la revista:
ANGIOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón