Tan Rubin, You Qiang, Yu Dongdong, Xiao Chushu, Adu-Amankwaah Joseph, Cui Jie, Zhang Ting
Department of Physiology, Basic Medical School, Xuzhou Medical University, Xuzhou, China.
School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.
Front Cardiovasc Med. 2022 Nov 30;9:945854. doi: 10.3389/fcvm.2022.945854. eCollection 2022.
Pulmonary hypertension (PH) is a life-threatening disease with complex pathogenesis. According to etiology, PH is divided into five major groups in clinical classification. However, pulmonary artery (PA) remodeling is their common feature, in addition to bone morphogenetic protein receptor type 2; it is elusive whether there are other novel common genes and similar underlying mechanisms. To identify novel common hub genes involved in PA remodeling at different PH groups, we analyzed mRNA-Seq data located in the general gene expression profile GSE130391 utilizing bioinformatics technology. This database contains PA samples from different PH groups of hospitalized patients with chronic thromboembolic pulmonary hypertension (CTEPH), idiopathic pulmonary artery hypertension (IPAH), and PA samples from organ donors without known pulmonary vascular diseases as control. We screened 22 hub genes that affect PA remodeling, most of which have not been reported in PH. We verified the top 10 common hub genes in hypoxia with Sugen-induced PAH rat models by qRT-PCR. The three upregulated candidate genes are and and the seven downregulated candidate genes are , and . , and were upregulated significantly in hypoxia with Sugen-induced PAH, while , and were upregulated significantly in hypoxia with Sugen-induced PAH. The DEGs detected by mRNA-Seq in hospitalized patients with PH are different from those in animal models. This study will provide some novel target genes to further study PH mechanisms and treatment.
肺动脉高压(PH)是一种发病机制复杂的危及生命的疾病。根据病因,PH在临床分类中分为五大类。然而,除了骨形态发生蛋白受体2型外,肺动脉(PA)重塑是它们的共同特征;是否存在其他新的共同基因和类似的潜在机制尚不清楚。为了确定不同PH组中参与PA重塑的新的共同枢纽基因,我们利用生物信息学技术分析了位于通用基因表达谱GSE130391中的mRNA-Seq数据。该数据库包含来自慢性血栓栓塞性肺动脉高压(CTEPH)、特发性肺动脉高压(IPAH)住院患者不同PH组的PA样本,以及来自无已知肺血管疾病的器官供体的PA样本作为对照。我们筛选出了22个影响PA重塑的枢纽基因,其中大多数在PH中尚未见报道。我们通过qRT-PCR在Sugen诱导的PAH大鼠低氧模型中验证了前10个共同枢纽基因。三个上调的候选基因是 和 ,七个下调的候选基因是 、 和 。 、 和 在Sugen诱导的PAH低氧中显著上调,而 、 和 在Sugen诱导的PAH低氧中显著上调。mRNA-Seq在PH住院患者中检测到的差异表达基因(DEGs)与动物模型中的不同。本研究将提供一些新的靶基因,以进一步研究PH的机制和治疗。