Nr1d1 inhibition mitigates intermittent hypoxia-induced pulmonary hypertension via Dusp1-mediated Erk1/2 deactivation and mitochondrial fission attenuation.

ABSTRACT: Intermittent hypoxia (IH) precipitates pulmonary vasoconstriction, culminating in the onset of pulmonary hypertension (PH) among individuals afflicted with sleep apnea. While Nuclear receptor subfamily 1 group D member 1 (Nr1d1) is progressively recognized as pivotal regulator of cellular physiology, the role in the pathogenesis of IH-induced PH remains largely uncharted. The expression of Nr1d1 was examined in IH-induced rodent PH and in IH-treated PASMCs. To elucidate the contribution of Nr1d1 to the development of IH-induced PH, we employed siRNA to modulate Nr1d1 expression in vitro and employed serotype 1 adeno-associated virus (AAV1) in vivo. Nr1d1 levels were elevated in IH-induced rodents PH lung tissues and IH-treated PASMCs. Knocking down Nr1d1 by AAV1 effectively inhibited PH pr

SUBMITTER: Pan Z 

PROVIDER: S-EPMC11522549 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature