Important Role of Endogenous Nerve Growth Factor Receptor in the Pathogenesis of Hypoxia-Induced Pulmonary Hypertension in Mice.
Chiaki GotenSoichiro UsuiShin-Ichiro TakashimaOto InoueKosei YamaguchiDaiki HashimukoYusuke TakedaAyano NomuraKenji SakataShuichi KanekoMasayuki TakamuraPublished in: International journal of molecular sciences (2023)
Pulmonary arterial hypertension (PAH) remains a disease with poor prognosis; thus, a new mechanism for PAH treatment is necessary. Circulating nerve growth factor receptor (Ngfr)-positive cells in peripheral blood mononuclear cells are associated with disease severity and the prognosis of PAH patients; however, the role of Ngfr in PAH is unknown. In this study, we evaluated the function of Ngfr using Ngfr gene-deletion (Ngfr -/- ) mice. To elucidate the role of Ngfr in pulmonary hypertension (PH), we used Ngfr -/- mice that were exposed to chronic hypoxic conditions (10% O 2 ) for 3 weeks. The development of hypoxia-induced PH was accelerated in Ngfr -/- mice compared to littermate controls. In contrast, the reconstitution of bone marrow (BM) in Ngfr -/- mice transplanted with wild-type BM cells improved PH. Notably, the exacerbation of PH in Ngfr -/- mice was accompanied by the upregulation of pulmonary vascular remodeling-related genes in lung tissue. In a hypoxia-induced PH model, Ngfr gene deletion resulted in PH exacerbation. This suggests that Ngfr may be a key molecule involved in the pathogenesis of PAH.
Keyphrases
- pulmonary hypertension
- growth factor
- wild type
- pulmonary arterial hypertension
- poor prognosis
- high fat diet induced
- bone marrow
- pulmonary artery
- induced apoptosis
- chronic obstructive pulmonary disease
- polycyclic aromatic hydrocarbons
- magnetic resonance imaging
- mesenchymal stem cells
- insulin resistance
- newly diagnosed
- magnetic resonance
- chronic kidney disease
- cell proliferation
- oxidative stress
- ejection fraction
- computed tomography
- acute respiratory distress syndrome
- endoplasmic reticulum stress
- cell death