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 patien...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/3/1868 |
| Summary: | 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<sup>−/−</sup>) mice. To elucidate the role of Ngfr in pulmonary hypertension (PH), we used Ngfr<sup>−/−</sup> mice that were exposed to chronic hypoxic conditions (10% O<sub>2</sub>) for 3 weeks. The development of hypoxia-induced PH was accelerated in Ngfr<sup>−/−</sup> mice compared to littermate controls. In contrast, the reconstitution of bone marrow (BM) in Ngfr<sup>−/−</sup> mice transplanted with wild-type BM cells improved PH. Notably, the exacerbation of PH in Ngfr<sup>−/−</sup> 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. |
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| ISSN: | 1661-6596 1422-0067 |