The circulatory small non-coding RNA landscape in community-acquired pneumonia on intensive care unit admission.


Journal

Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777

Informations de publication

Date de publication:
08 2021
Historique:
revised: 10 02 2021
received: 05 12 2020
accepted: 12 02 2021
pubmed: 18 7 2021
medline: 19 2 2022
entrez: 17 7 2021
Statut: ppublish

Résumé

Community-acquired pneumonia (CAP) is a major cause of sepsis. Despite several clinical trials targeting components of the inflammatory response, no specific treatment other than antimicrobial therapy has been approved. This argued for a deeper understanding of sepsis immunopathology, in particular factors that can modulate the host response. Small non-coding RNA, for example, micro (mi)RNA, have been established as important modifiers of cellular phenotypes. Notably, miRNAs are not exclusive to the intracellular milieu but have also been detected extracellular in the circulation with functional consequences. Here, we sought to determine shifts in circulatory small RNA levels of critically ill patients with CAP-associated sepsis and to determine the influence of clinical severity and causal pathogens on small RNA levels. Blood plasma was collected from 13 critically ill patients with sepsis caused by CAP on intensive care unit admission and from 5 non-infectious control participants. Plasma small RNA-sequencing identified significantly altered levels of primarily mature miRNAs in CAP relative to controls. Pathways analysis of high or low abundance miRNA identified various over-represented cellular biological pathways. Analysis of small RNA levels against common clinical severity and inflammatory parameters indices showed direct and indirect correlations. Additionally, variance of plasma small RNA levels in CAP patients may be explained, at least in part, by differences in causal pathogens. Small nuclear RNA levels were specifically altered in CAP due to Influenza infection in contrast to Streptococcus pneumoniae infection. Pathway analysis of plasma miRNA signatures unique to Influenza or Streptococcus pneumoniae infections showed enrichment for specific proteoglycan, cell cycle, and immunometabolic pathways.

Identifiants

pubmed: 34272809
doi: 10.1111/jcmm.16406
pmc: PMC8358855
doi:

Substances chimiques

MicroRNAs 0
RNA, Small Untranslated 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

7621-7630

Informations de copyright

© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

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Auteurs

Hina N Khan (HN)

Center for Experimental Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, The Netherlands.
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.

Aldo Jongejan (A)

Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.

Lonneke A van Vught (LA)

Center for Experimental Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, The Netherlands.

Janneke Horn (J)

Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.

Marcus J Schultz (MJ)

Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.
Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand.

Aeilko H Zwinderman (AH)

Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.

Olaf L Cremer (OL)

Department of Intensive Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Marc J Bonten (MJ)

Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.

Tom van der Poll (T)

Center for Experimental Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, The Netherlands.
Division of Infectious Diseases, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Brendon P Scicluna (BP)

Center for Experimental Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, The Netherlands.
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands.

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