Implication of proliferation gene biomarkers in pulmonary hypertension

[摘要] Objective/Background Proliferation is a widely recognized trigger for pulmonary hypertension (PH), a life-threatening, progressive disorder of pulmonary blood vessels. This study was aimed to identify some proliferation associated genes/targets for better comprehension of PH pathogenesis. Methods Human pulmonary arterial smooth muscle cells (hPASMCs) were cultured in the presence or absence of human recombinant platelet derived growth factor (rhPDGF)-BB. Cells were collected for metabolomics or transcriptomics study. Gene profiling of lungs of PH rats after hypoxia exposure or of PH patients were retrieved from GEO database. Results 90 metabolites (VIP score >1, fold change >2 or 2 or <0.5 and p  < .05). 152 differentially expressed MAGs were then determined, out of which 9 hub genes (IL6, CXCL8, CCL2, CXCR4, CCND1, PLAUR, PLAU, HBEGF and F3) were defined as core proliferation associated hub genes in protein proten interaction analysis. In addition, the hub gene-based LASSO model can predict the occurrence of PH (AUC = 0.88). The expression of CXCR4, as one of the hub genes, was positively correlated to immune cell infiltrates. Conclusion Our findings revealed some key proliferation associated genes in PH, which provide the crucial information concerning complex metabolic reprogramming and inflammatory modulation in response to proliferation signals and might offer therapeutic gains for PH.

[学科分类] 机械工程学

[关键词] metabolism associated genes;metabolomics;proliferation;pulmonary hypertension;transcriptomics