ArticleTranslational pediatrics2025
Gene and metabolite changes triggered by downregulation of JUNB and ZNF281 in idiopathic pulmonary arterial hypertension: potential mechanisms revealed by multi-omics study.
Article in Translational pediatrics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease causing right heart failure. Idiopathic PAH (IPAH), a type of PAH with unknown causes, has a particularly poor prognosis. Current targeted therapies are insufficient, highlighting the need for new therapeutic targets and biomarkers. This study aims to identify potential metabolic biomarkers and dysregulated pathways for the diagnosis and treatment of IPAH through integrated metabolomic and transcriptomic analyses. Methods: This study enrolled PAH patients [2023-2024] and collected pretreatment blood samples, using healthy children as controls. RNA sequencing analyzed gene expression in peripheral blood mononuclear cells (PBMCs), and liquid chromatography-mass spectrometry (LC-MS) detected blood metabolites. Metabolites were identified via multiple databases, and bioinformatics analyses [principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA)] explored PAH's molecular mechanisms. Results: In PAH patients, 1,629 differentially expressed genes (DEGs) were found, with 802 upregulated and 827 downregulated genes, enriched in cell cycle regulation, stress response, and mitochondrial dysfunction. Metabolomics showed 30 upregulated and 29 downregulated metabolites, mainly in amino acid and energy metabolism. Key genes like Conclusions: The study underscores the intimate connection between transcription factor (e.g., JUNB, ZNF281)-regulated gene expression (e.g.,
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