Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis

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 Ga...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rumienczyk I, Kulecka M, Ostrowski J, Mar D, Bomsztyk K, Standage SW, Mikula M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	sepsis rna-seq reactome murine model Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/7909e69567084b518fc25a2ea3902a79
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7909e69567084b518fc25a2ea3902a79
record_format	dspace
spelling	oai:doaj.org-article:7909e69567084b518fc25a2ea3902a792021-12-02T14:54:17ZMulti-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis1178-7031https://doaj.org/article/7909e69567084b518fc25a2ea3902a792021-06-01T00:00:00Zhttps://www.dovepress.com/multi-organ-transcriptome-dynamics-in-a-mouse-model-of-cecal-ligation--peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Izabela 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 michal.mikula@pib-nio.plPurpose: 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 modelRumienczyk IKulecka MOstrowski JMar DBomsztyk KStandage SWMikula MDove Medical Pressarticlesepsisrna-seqreactomemurine modelPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 2377-2388 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sepsis rna-seq reactome murine model Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	sepsis rna-seq reactome murine model Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Rumienczyk I Kulecka M Ostrowski J Mar D Bomsztyk K Standage SW Mikula M Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis
description	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 michal.mikula@pib-nio.plPurpose: 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
format	article
author	Rumienczyk I Kulecka M Ostrowski J Mar D Bomsztyk K Standage SW Mikula M
author_facet	Rumienczyk I Kulecka M Ostrowski J Mar D Bomsztyk K Standage SW Mikula M
author_sort	Rumienczyk I
title	Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis
title_short	Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis
title_full	Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis
title_fullStr	Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis
title_full_unstemmed	Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis
title_sort	multi-organ transcriptome dynamics in a mouse model of cecal ligation and puncture-induced polymicrobial sepsis
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/7909e69567084b518fc25a2ea3902a79
work_keys_str_mv	AT rumienczyki multiorgantranscriptomedynamicsinamousemodelofcecalligationandpunctureinducedpolymicrobialsepsis AT kuleckam multiorgantranscriptomedynamicsinamousemodelofcecalligationandpunctureinducedpolymicrobialsepsis AT ostrowskij multiorgantranscriptomedynamicsinamousemodelofcecalligationandpunctureinducedpolymicrobialsepsis AT mard multiorgantranscriptomedynamicsinamousemodelofcecalligationandpunctureinducedpolymicrobialsepsis AT bomsztykk multiorgantranscriptomedynamicsinamousemodelofcecalligationandpunctureinducedpolymicrobialsepsis AT standagesw multiorgantranscriptomedynamicsinamousemodelofcecalligationandpunctureinducedpolymicrobialsepsis AT mikulam multiorgantranscriptomedynamicsinamousemodelofcecalligationandpunctureinducedpolymicrobialsepsis
_version_	1718389392018505728

Multi-Organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture-Induced Polymicrobial Sepsis

Ejemplares similares