Nur77 induced by HIF-1α mediates vascular remodeling in hypoxic pulmonary hypertension.
Cell Mol Biol (Noisy-le-grand)
; 70(6): 233-237, 2024 Jun 05.
Article
en En
| MEDLINE
| ID: mdl-38836656
ABSTRACT
Nur77 is a member of the NR4A subfamily of orphan nuclear receptors that is expressed and has a function within the immune system. This study aimed to investigate the role of Nur77 in hypoxic pulmonary hypertension. SPF male SD rats were exposed in hypobaric chamber simulating 5000 m high altitude for 0, 3, 7, 14, 21 or 28 days. Rat pulmonary artery smooth muscle cells (RPASMCs) were cultured under normoxic conditions (5% CO2-95% ambient air) or hypoxic conditions (5% O2 for 6 h, 12 h, 24 h, 48 h). Hypoxic rats developed pulmonary arterial remodeling and right ventricular hypertrophy with significantly increased pulmonary arterial pressure. The levels of Nur77, HIF-1α and PNCA were upregulated in pulmonary arterial smooth muscle from hypoxic rats. Silencing of either Nur77 or HIF-1α attenuated hypoxia-induced proliferation. Silencing of HIF-1α down-regulated Nur77 protein level, but Nur77 silence did not reduce HIF-1α. Nur77 was not con-immunoprecipitated with HIF-1α. This study demonstrated that Nur77 acted as a downstream regulator of HIF-1α under hypoxia, and plays a critical role in the hypoxia-induced pulmonary vascular remodeling, which is regulated by HIF-1α. Nur77 maybe a novel target of HPH therapy.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Arteria Pulmonar
/
Subunidad alfa del Factor 1 Inducible por Hipoxia
/
Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares
/
Remodelación Vascular
/
Hipertensión Pulmonar
/
Hipoxia
Límite:
Animals
Idioma:
En
Revista:
Cell Mol Biol (Noisy-le-grand)
/
Cell. mol. biol. (Online)
/
Cellular and molecular biology (Online)
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2024
Tipo del documento:
Article
País de afiliación:
China