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Role of Sphingolipid pathways in the pathobiology of PAH

Role of Sphingolipid pathways in the pathobiology of PAH
鞘脂通路在 PAH 病理学中的作用
批准号:
10645008
负责人:
Roberto F. Machado
金额:
$68.8万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
未结题
起止时间:
2016-01-05 至 2025-06-30

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中文摘要
翻译
摘要 肺动脉高压(PAH)是一种罕见的、使人衰弱的致命疾病,目前尚无治疗方法 可用的治疗方法。有令人信服的证据表明,鞘氨醇激酶1/S1P信号轴是一种新的和 PAH的治疗靶点。促进翻译目前在体内和体外的观察作用 关于PAH病理生物学中S1P依赖信号的研究,这一建议将探索鞘氨醇 Kinase1/S1P信号轴调节PAH中的生理、细胞和分子通路,从而导致 肺血管重塑。SA1试图确定lncRNA Khps1在miR-1和SPHK1表达中的作用 促进肺血管重塑。SA2试图定义lncRNA通过哪些分子机制 KHPS1/SPHK1调节肺动脉平滑肌细胞线粒体动力学。SA3将调查 SPHK1在肺血管发育中染色质异常重塑及基因表达中的作用 改建。
英文摘要
ABSTRACT Pulmonary arterial hypertension (PAH), a rare, debilitating and fatal disease for which there is currently no available cure. There is compelling evidence that the Sphingosine kinase1/S1P signaling axis is a novel and therapeutic target for PAH. To facilitate the translation of current in vivo and in vitro observations on the role of S1P dependent signaling in PAH pathobiology, this proposal will explore the hypothesis that the Sphingosine kinase1/S1P signaling axis regulates physiologic, cellular and molecular pathways in PAH that result in pulmonary vascular remodeling. SA1 seeks to define the role of LncRNA Khps1 in miR-1 and SPHK1 expression and promoting pulmonary vascular remodeling. SA2 seeks to define molecular mechanisms by which LncRNA Khps1/SPHK1 regulate pulmonary artery smooth muscle cell mitochondrial dynamics. SA3 will investigate the role of SPHK1 in aberrant chromatin remodeling and gene expression in the development of pulmonary vascular remodeling.
期刊论文(26)
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会议论文
DOI: 10.1016/j.trsl.2018.01.007
发表时间: 2018-07
期刊: Translational research : the journal of laboratory and clinical medicine
影响因子: --
作者: [Saraf SL, Sysol JR, Susma A, Setty S, Zhang X, Gudehithlu KP, Arruda JAL, Singh AK, Machado RF, Gordeuk VR]
通讯作者: Gordeuk VR
DOI: 10.1111/nyas.13037
发表时间: 2016-03
期刊: Annals of the New York Academy of Sciences
影响因子: 5.2
作者: [Fraidenburg DR, Machado RF]
通讯作者: Machado RF
DOI: 10.1177/2045894018773049
发表时间: 2018-04
期刊: Pulmonary circulation
影响因子: 2.6
作者: [Duarte JD, Kansal M, Desai AA, Riden K, Arwood MJ, Yacob AA, Stamos TD, Cavallari LH, Zamanian RT, Shah SJ, Machado RF]
通讯作者: Machado RF
DOI: 10.1007/s12013-021-01005-9
发表时间: 2021-09
期刊: Cell biochemistry and biophysics
影响因子: 2.6
作者: [Ebenezer DL, Ramchandran R, Fu P, Mangio LA, Suryadevara V, Ha AW, Berdyshev E, Van Veldhoven PP, Kron SJ, Schumacher F, Kleuser B, Natarajan V]
通讯作者: Natarajan V
6
    NAD-dependent Signaling and Pulmonary Vascular Remodeling in PAH
    NAD-dependent Signaling and Pulmonary Vascular Remodeling in PAH
    Role of Sphingolipid pathways in the pathobiology of PAH
    Role of Sphingolipid Pathways in the Pathobiology of PAH
    • 批准号:
      9055416
    • 项目类别:
    • 资助金额:
      $46.97万
    • 财政年份:
      2016
    • 负责人:
      Roberto F. Machado
    • 依托单位:
    海外基金