Histone demethylase JARID1B regulates proliferation and migration of pulmonary arterial smooth muscle cells in mice with chronic hypoxia-induced pulmonary hypertension via nuclear factor-kappa B (NFkB)
Histone demethylase JARID1B regulates proliferation and migration of pulmonary arterial smooth muscle cells in mice with chronic hypoxia-induced pulmonary hypertension via nuclear factor-kappa B (NFkB)
复制标题
组蛋白去甲基化酶 JARID1B 通过核因子 kappa B (NFkB) 调节慢性缺氧诱导的肺动脉高压小鼠肺动脉平滑肌细胞的增殖和迁移
DOI：
10.1016/j.carpath.2018.07.004
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发表时间：
2018-11-01
影响因子：
3.7
通讯作者：
Cao, Junxian
中科院分区：
文献类型：
--
作者：
Li, Yuanshi;Liu, Sining;Cao, Junxian
慢性缺氧性肺动脉高压（PH）是一种以肺动脉压升高为特征的疾病，其由肺部疾病或体内缺氧引起。肺血管细胞如肺动脉内皮细胞（PAECs）和肺动脉平滑肌细胞（PASMCs）的过度增殖在PH的发病机制中起关键作用。表观遗传机制在PH的病因学中起着至关重要的作用。在这项研究中，我们研究了组蛋白去甲基化酶jumonji AT丰富的相互作用域1B（JARID 1B）在调节慢性缺氧诱导的PH条件下血管平滑肌细胞增殖中可能发挥的作用。定量聚合酶链反应分析显示PH大鼠PASMCs中JARID 1 B的表达升高，与核因子-κ B（NFk B）表达升高呈正相关。进一步的体外功能研究表明，JARID 1B的过表达增加了PASMCs的增殖和迁移。其被NFkB的耗竭抑制。全基因组转录分析表明，JARID 1B通过直接结合其启动子来调节NF κ B信号通路。我们还发现，JARID I B通过NF κ B B信号间接调节血管内皮生长因子的表达，因此也可能在控制PAEC中发挥关键作用，导致PH中血管结构的变化。我们的研究结果可能导致进一步研究JARID 1 B在PH病因中的作用，因此可能导致慢性缺氧诱导的肺动脉高压的潜在治疗靶点。(C)2018由Elsevier Inc.出版
Chronic hypoxia-induced pulmonary hypertension (PH) is a disorder that is characterized by increased pulmonary arterial pressure resulting from lung diseases or shortage of oxygen in the body. Excess proliferation of pulmonary vascular cells such as pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) plays a critical role in the pathogenesis of PH. Recent evidence indicates that, in addition to genetic predisposition and environmental factors. epigenetic mechanisms play a pivotal role in etiology of PH. In this study, we investigated the possible role played by jumonji AT-rich interactive domain 1B (JARID1B), a histone demethylase, in regulating the proliferation of vascular smooth muscle cells in chronic hypoxia-induced PH condition. Quantitative polymerase chain reaction analysis of samples from rats with PH showed an elevated expression of JARID1B in their PASMCs, positively correlating with increased nuclear factor-kappa B (NFkB) expression. Further functional studies in vitro indicated that overexpression of JARID1B increased the proliferation and migration of PASMCs. which were inhibited by depletion of NFkB. Genomewide transcriptional analysis revealed that the JARID1B regulated NFkB signaling pathway by directly binding to its promoter. We have also shown that JARID I B indirectly regulates the expression of vascular endothelial growth factor via NFkB signaling and hence may also play a crucial role in controlling PAECs, leading to changes in vascular architecture in PH. Our findings could lead to further studies on the role of JARID1B in PH etiology and therefore could lead to a potential therapeutic target for chronic hypoxia induced pulmonary hypertension. (C) 2018 Published by Elsevier Inc.