プロテオミクスおよびゲノム解析に基づく敗血症関連肺傷害における分子状水素の標的としてのAPOA2の同定
This study integrated quantitative proteomics from a sepsis mouse model with mRNA sequencing data to identify molecular hydrogen (H2) target biomarkers at both protein and transcript levels. Functional pathway analysis and module correlation analysis were applied to pinpoint differentially expressed genes most relevant to disease progression. APOA2 emerged as a shared biomarker across proteomics and transcriptomics datasets. Causal relationships between APOA2 and sepsis phenotype were evaluated through expression quantitative trait locus (eQTL) mapping, genome-wide association study (GWAS) data, summary-data-based Mendelian randomization (SMR), and two-sample and drug-target Mendelian randomization analyses. Protein quantitative trait loci (pQTLs) were additionally incorporated into the protein-level analysis. HDL and type 2 diabetes were found to share causal links with sepsis. Animal experiments corroborated the computational findings, supporting APOA2 as a protective, causally relevant target mediating H2 effects in sepsis-related lung injury.
APOA2 protein and mRNA act as causally protective biomarkers mediating H2 effects in sepsis; modulation of APOA2 expression influences sepsis progression, with HDL metabolism and type 2 diabetes pathways identified as related causal factors.
This study is at the animal-experiment stage. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).
See also:
https://h2-papers.org/en/papers/37511084