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

Author:

Goten ChiakiORCID,Usui Soichiro,Takashima Shin-ichiro,Inoue Oto,Yamaguchi Kosei,Hashimuko Daiki,Takeda Yusuke,Nomura Ayano,Sakata Kenji,Kaneko Shuichi,Takamura MasayukiORCID

Abstract

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.

Funder

Ministry of Education, Culture, Sports, Science, and Technology, Japan

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference27 articles.

1. Mechanisms of disease: Pulmonary arterial hypertension;Schermuly;Nat. Rev. Cardiol.,2011

2. Pathology of pulmonary hypertension;Tuder;Clin. Chest Med.,2007

3. Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension;Rabinovitch;Circ. Res.,2014

4. Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension;Diller;Circulation,2008

5. Implantation of mesenchymal stem cells overexpressing endothelial nitric oxide synthase improves right ventricular impairments caused by pulmonary hypertension;Horimoto;Circulation,2006

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3