Important Role of Endogenous Nerve Growth Factor Receptor in the Pathogenesis of Hypoxia-Induced Pulmonary Hypertension in Mice.

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) 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.