Hydrogen Therapy Targets New Protein for Sepsis Lung Injury Treatment
- Authors
- Yuanlin Wang, Yan Fan, Yi Jiang, Enquan Wang, Yu Song, Hongguang Chen, Feier Wu, Keliang Xie, Yonghao Yu
- Journal
- International Journal of Molecular Sciences
- Year
- 2023
- DOI
- 10.3390/ijms241411325
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis
- Body System
- Respiratory
TL;DR
Researchers identified a protein and gene, Apoa2, that may protect against sepsis and could be a potential target for hydrogen (H2) treatments.
Key Finding
APOA2 protein was identified as a potential molecular target through which hydrogen gas may exert protective effects against sepsis-related lung injury, based on integrated analysis of mouse protein and gene data.
Summary
Researchers used computer analysis of protein and gene data from mice with sepsis (a life-threatening infection response) to identify which molecules hydrogen gas might target. They found that a protein called APOA2 appears to be involved in how sepsis develops and may be a key point where hydrogen could help protect the lungs. The study combined multiple types of genetic analysis to suggest that APOA2 plays a causal role in sepsis, and that adjusting its levels might reduce sepsis-related damage.
Practical Takeaway
This is early-stage research in mice that identifies a theoretical mechanism for how hydrogen might help with sepsis, but it does not yet demonstrate that hydrogen water or hydrogen gas helps people with sepsis. Human studies would be needed to determine if targeting APOA2 actually translates to clinical benefit. The findings are promising for future research directions but cannot guide treatment decisions at this time.
Abstract
Target biomarkers for H2 at both the protein and genome levels are still unclear. In this study, quantitative proteomics acquired from a mouse model were first analyzed. At the same time, functional pathway analysis helped identify functional pathways at the protein level. Then, bioinformatics on mRNA sequencing data were conducted between sepsis and normal mouse models. Differential expressional genes with the closest relationship to disease status and development were identified through module correlation analysis. Then, common biomarkers in proteomics and transcriptomics were extracted as target biomarkers. Through analyzing expression quantitative trait locus (eQTL) and genome-wide association studies (GWAS), colocalization analysis on Apoa2 and sepsis phenotype was conducted by summary-data-based Mendelian randomization (SMR). Then, two-sample and drug-target, syndrome Mendelian randomization (MR) analyses were all conducted using the Twosample R package. For protein level, protein quantitative trait loci (pQTLs) of the target biomarker were also included in MR. Animal experiments helped validate these results. As a result, Apoa2 protein or mRNA was identified as a target biomarker for H2 with a protective, causal relationship with sepsis. HDL and type 2 diabetes were proven to possess causal relationships with sepsis. The agitation and inhibition of Apoa2 were indicated to influence sepsis and related syndromes. In conclusion, we first proposed Apoa2 as a target for H2 treatment.