Journal of Inflammation Research (Jun 2021)
Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis
Abstract
Izabela Rumienczyk,1 Maria Kulecka,1,2 Jerzy Ostrowski,1,2 Daniel Mar,3 Karol Bomsztyk,3 Stephen W Standage,4,5 Michal Mikula1 1Maria Sklodowska-Curie National Research Institute of Oncology, Department of Genetics, Warsaw, 02-781, Poland; 2Centre for Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, 01-813, Poland; 3UW Medicine South Lake Union, University of Washington, Seattle, WA, 98109, USA; 4Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 5Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USACorrespondence: Michal MikulaMaria Sklodowska-Curie National Research Institute of Oncology, Department of Genetics, Warsaw, 02-781, PolandTel +48225462655Email [email protected]: 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.Keywords: sepsis, RNA-seq, reactome, murine model
