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

Chiaki Goten, Soichiro Usui, Shin-Ichiro Takashima, Oto Inoue, Kosei Yamaguchi, Daiki Hashimuko, Yusuke Takeda, Ayano Nomura, Kenji Sakata, Shuichi Kaneko, Masayuki Takamura

International journal of molecular sciences 2023 Jan 18

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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% O2) 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.

Citation

Chiaki Goten, Soichiro Usui, Shin-Ichiro Takashima, Oto Inoue, Kosei Yamaguchi, Daiki Hashimuko, Yusuke Takeda, Ayano Nomura, Kenji Sakata, Shuichi Kaneko, Masayuki Takamura. Important Role of Endogenous Nerve Growth Factor Receptor in the Pathogenesis of Hypoxia-Induced Pulmonary Hypertension in Mice. International journal of molecular sciences. 2023 Jan 18;24(3)