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Updated: Nov 2, 2025
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis
Izabela Rumienczyk1, Maria Kulecka1,2, Jerzy Ostrowski1,2
1Maria Sklodowska-Curie National Research Institute of Oncology, Department of Genetics, Warsaw, 02-781, Poland.
Purpose:
During sepsis, an excessive inflammatory immune reaction contributes to multi-organ dysfunction syndrome (MODS), a critical condition associated with high morbidity and mortality; however, the molecular mechanisms driving MODS remain elusive.
Methods:
We used RNA sequencing to characterize transcriptional changes in the early phase of sepsis, at 6, 12, 24 hour time points in lung, kidney, liver, and heart tissues, in a cecal ligation and puncture (CLP)-induced polymicrobial sepsis murine model.
Results:
The CLP surgery induced significant changes (adj. p-value<0.05) in expression of hundreds of transcripts in the four organs tested, with the highest number exceeding 2,000 differentially expressed genes (DEGs) in all organs at 12 hours post-CLP. Over-representation analysis by functional annotations of DEGs to the Reactome database revealed the immune system, hemostasis, lipid metabolism, signal transduction, and extracellular matrix remodeling biological processes as significantly altered in at least two organs, while metabolism of proteins and RNA were revelaed as being liver tissue specific in the early phase of sepsis.
Conclusion:
RNA sequencing across organs and time-points in the CLP murine model allowed us to study the trajectories of transcriptome changes demonstrating alterations common across multiple organs as well as biological pathways altered in an organ-specific manner. These findings could pave new directions in the research of sepsis-induced MODS and indicate new sepsis treatment strategies.
Insights
This study used RNA sequencing to reveal molecular changes in sepsis-induced multi-organ dysfunction syndrome (MODS). Key immune and metabolic pathways were altered across organs, offering new treatment targets.
Area of Science:
- Molecular Biology
- Genomics
- Sepsis Research
Background:
- Sepsis triggers excessive inflammation, leading to multi-organ dysfunction syndrome (MODS).
- The molecular mechanisms underlying MODS remain poorly understood.
- High morbidity and mortality rates underscore the need for research into sepsis pathogenesis.
Purpose of the Study:
- To characterize early-phase transcriptional changes in multiple organs during polymicrobial sepsis.
- To identify molecular mechanisms driving sepsis-induced multi-organ dysfunction syndrome (MODS).
- To uncover potential therapeutic targets for sepsis treatment.
Main Methods:
- Utilized RNA sequencing to analyze transcriptomic profiles in murine sepsis model.
- Examined changes in lung, kidney, liver, and heart tissues at 6, 12, and 24 hours post-cecal ligation and puncture (CLP).
- Performed over-representation analysis of differentially expressed genes (DEGs) using the Reactome database.
Main Results:
- Cecal ligation and puncture (CLP) induced significant transcriptomic alterations in all four organs.
- Over 2,000 differentially expressed genes (DEGs) were identified in all organs by 12 hours post-CLP.
- Commonly altered pathways included immune response, hemostasis, and lipid metabolism; protein and RNA metabolism were liver-specific.
Conclusions:
- RNA sequencing across organs and time points elucidated dynamic transcriptome changes in sepsis.
- Identified both shared and organ-specific molecular pathways affected by sepsis.
- Findings provide novel insights into sepsis-induced MODS and suggest potential therapeutic strategies.
