Integration of transcriptomics, proteomics, phosphoproteomics analysis for characterization of pulmonary arterial hypertension in Chinese people

Abstract

Background Pulmonary arterial hypertension (PAH), a fatal disease, is characterized by pulmonary vascular remodeling and vascular resistance. However, the molecular mechanisms underlying the pathogenesis of PAH remained to be incompletely understood. Methods RNA-seq, 4D Lable-free proteomics and phosphoproteomics were used to detect the levels of mRNA, proteins, and phosphoproteins in lung tissues from PAH patients, respectively. Parallel reaction monitoring (PRM) was carried out to verify the expression of the differentially expressed proteins. Results Totally, 967 differentially expressed genes (|log2FoldChange|>1 and p < 0.05), 764 differentially expressed proteins and 411 phosphoproteins were observed after data filtering (|log2FoldChange|>1 and p < 0.05) in lung tissues of PAH patients as compared with the control group. Integrated analysis of the three omic measures revealed that the biological processes involving inflammation, ion channel and metabolism were closely associated with PAH. Several signaling pathways, such as ferroptosis, HIF-1, PI3K-AKT, and Rap1 might be related to the development of PAH. Conclusions This study combined multi-omics characteristic profiling to find out the changed genes or proteins that contributed to a detailed pathogenic of PAH. It would have the benefit of looking for the novel and effective treatment targets and therapeutic drugs to PAH patients.