Lv Zhenchun, Jiang Rong, Hu Xiaoyi, Zhao Qinhua, Sun Yuanyuan, Wang Lan, Li Jinling, Miao Yuqing, Wu Wenhui, Yuan Ping
Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, School of Medicine, Shanghai, China.
Institute of Bismuth Science, University of Shanghai for Science and Technology, Shanghai, China.
Ann Transl Med. 2021 May;9(10):879. doi: 10.21037/atm-21-2040.
At present, the role of lncRNAs in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH) is not fully understood. This study aimed to explore differences in the hypoxia-induced expression of lncRNAs and their potential role in multiple pulmonary artery cells.
LncRNA expression in pulmonary artery smooth muscle cells (PASMCs), pulmonary microvascular endothelial cells (PMECs), and pericytes (PCs) was analyzed by high-throughput sequencing and compared between normoxic and hypoxic cells. Bioinformatics analysis was conducted to predict their functions.
PASMCs, PMECs, and PCs displayed 275 (140 upregulated), 251 (162 upregulated), and 290 (176 upregulated) different lncRNAs, respectively. Among these, lncRNA TUG1 levels increased in PASMCs and PCs but decreased in PMECs. Bioinformatics analysis indicated that lncRNA TUG1 might target miR-145-5p, thereby affecting SOX4 and BMF expression, and could also regulate miR-129-5p levels to affect CYP1B1 and VCP expression. It could also regulate miR-138-5p levels to affect KCNK3 and RHOC expression.
Hypoxia exposure of vascular cells resulted in differential expression of lncRNAs, especially lncRNA TUG1, which showed significant abnormal expression in all three types of vascular cells under hypoxia. Our results suggested that abnormal expression of lncRNA TUG1 might be involved in the regulation of pulmonary vascular cell function under hypoxia.
目前,长链非编码核糖核酸(lncRNAs)在缺氧诱导的肺动脉高压(HPH)发病机制中的作用尚未完全明确。本研究旨在探讨lncRNAs在缺氧诱导下的表达差异及其在多种肺动脉细胞中的潜在作用。
通过高通量测序分析肺动脉平滑肌细胞(PASMCs)、肺微血管内皮细胞(PMECs)和周细胞(PCs)中lncRNA的表达,并比较常氧和缺氧细胞之间的差异。进行生物信息学分析以预测其功能。
PASMCs、PMECs和PCs分别显示出275种(140种上调)、251种(162种上调)和290种(176种上调)不同的lncRNAs。其中,lncRNA TUG1在PASMCs和PCs中的水平升高,但在PMECs中降低。生物信息学分析表明,lncRNA TUG1可能靶向miR-145-5p,从而影响SOX4和BMF的表达,还可能调节miR-129-5p的水平以影响CYP1B1和VCP的表达。它还可能调节miR-138-5p的水平以影响KCNK3和RHOC的表达。
血管细胞缺氧暴露导致lncRNAs表达差异,尤其是lncRNA TUG1,其在缺氧条件下在所有三种类型的血管细胞中均表现出明显的异常表达。我们的结果表明,lncRNA TUG1的异常表达可能参与缺氧条件下肺血管细胞功能的调节。