机构：[1]Department of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China[2]Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Institute of Respiratory Medicine, Beijing, People’s Republic of China[3]Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China[4]Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China[5]Department of Pulmonary and Critical Care Medicine, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China首都医科大学宣武医院[6]Department of Physiology, Capital Medical University, Beijing, People’s Republic of China[7]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China[8]Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease, which is often underpinned by vascular remodeling. Pulmonary arterial smooth muscle cells (PASMCs) are the main participants in vascular remodeling. However, their biological role in CTEPH is not entirely clear. In the present study, we analyzed the whole epigenome-wide DNA methylation profile of cultured PASMCs from CTEPH and control cell lines with the Illumina Human Methylation 450K BeadChip. A total of 6,829 significantly differentially methylated probes (DMPs) were detected between these two groups. Among these, 4.246 DMPs were hypermethylated. while 2,583 DMPs were hypomethylated. The functional enrichment analysis of 1,743 DMPs in the promoter regions and corresponding genes indicated that DNA hypermethylation and hypomethylation might be involved in the regulation of genes that have multifarious biological roles, including roles in cancer-related diseases, the regulation of the actin cytoskeleton, cell adhesion, and pattern specification processes. The observed methylations were categorized into the most important functions, including those involved in cell proliferation, immunity, and migration. We speculate that these methylations were most likely involved in the possible pathophysiology of CTEPH. Gene interaction analysis pertaining to signal networks confirmed that PIK3CA and PIK3R1 were important mediators in these whole networks. The mRNA levels of PIK3CA, HIC1, and SSH1 were verified by qPCR and corresponded with DNA methylation differences. Understanding epigenetic features associated with CTEPH may provide new insights into the mechanism that underlie this condition.
基金：
National Natural Science Foundation of China (81200042 and 81300044), Beijing Natural Science Foundation(7154198 and 7162069),
Beijing Nova Program (Z121107002512021),
Cooperation Program between Capital Medical University and Beijing Tiantan Hospital (17JL50),
the Capital’s Funds for Health Improvement and Research(CFH 2018-2-2042).
第一作者机构：[1]Department of Clinical Laboratory, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China[2]Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Institute of Respiratory Medicine, Beijing, People’s Republic of China
通讯作者：
通讯机构：[*1]Dept. of Neurosurgery, Beijing Tiantan Hospital, 6 Tiantan Xi li, Beijing, 100050, China
推荐引用方式(GB/T 7714)：
Ying Wang ,Xiaoxi Huang ,Dong Leng ,et al.DNA methylation signatures of pulmonary arterial smooth muscle cells in chronic thromboembolic pulmonary hypertension[J].PHYSIOLOGICAL GENOMICS.2018,50(5):313-322.doi:10.1152/physiolgenomics.00069.2017.
