Functional analysis of NGFR positive cells in pulmonary arterial hypertension

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K17670
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kanazawa University
• Principal Investigator: GOTEN CHIAKI 金沢大学, 医薬保健学総合研究科, 特任助教 (80802818)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 肺動脈性肺高血圧症 / 神経成長因子受容体 / 肺血管リモデリング

Outline of Final Research Achievements

In this study, we confirmed that NGFR-positive cells were significantly increased in peripheral blood in patients with pulmonary hypertension compared to healthy subjects. Furthermore, NGFR-positive cells were found to be correlated with hemodynamics (mean pulmonary artery pressure, cardiac index, pulmonary vascular resistance) in pulmonary hypertension, and it was confirmed that NGFR-positive cells in peripheral blood increased in more severe pulmonary hypertension.
Additionally, NGFR gene-deficient (KO) mice exhibited worsening of hypoxia-induced pulmonary hypertension compared to WT mice. On the other hand, NGFRKO mice transplanted with WT bone marrow showed improved pulmonary vascular remodeling. These results suggested that NGFR-positive cells may have a protective effect on the pathogenesis of pulmonary hypertension.

Free Research Field

肺高血圧症

Academic Significance and Societal Importance of the Research Achievements

肺高血圧症における間葉系幹細胞の機能的役割は十分に解明されていない。本試験では、間葉系幹細胞の中でも、多分化能、増殖能に優れたNGFR陽性細胞に着目し、臨床研究にてNGFR陽性細胞と肺高血圧症の重症度および予後との関連性を明らかにし、基礎研究にてNGFR遺伝子欠損マウスを用いて、肺高血圧症の病態形成におけるNGFR陽性細胞の役割について検討した。本研究を通して、肺高血圧症における間葉系幹細胞の関連性を明らかにし、新たな肺高血圧症の治療の切り口となる可能性を示した。今後、NGFR陽性細胞の肺血管リモデリングに関与する機序解明にむけ、さらなる検討が必要である。