Transcriptomic investigation reveals donor-specific gene signatures in human lung transplants.

Extracorporeal Circulation Humans Lung Lung Transplantation Perfusion Tissue Donors Transcriptome

Journal

The European respiratory journal
ISSN: 1399-3003
Titre abrégé: Eur Respir J
Pays: England
ID NLM: 8803460

Informations de publication

Date de publication:
04 2021
Historique:
received: 14 02 2020
accepted: 05 10 2020
pubmed: 31 10 2020
medline: 3 7 2021
entrez: 30 10 2020
Statut: epublish

Résumé

Transplantation of lungs from donation after circulatory death (DCD) in addition to donation after brain death (DBD) became routine worldwide to address the global organ shortage. The development of Tissue biopsies from human DBD (n=177) and DCD (n=65) donor lungs, assessed with or without EVLP, were collected at the end of cold ischaemic time. All samples were processed with microarray assays. Gene expression, network and pathway analyses were performed using R, Ingenuity Pathway Analysis and STRING. Results were validated with protein assays, multiple logistic regression and 10-fold cross-validation. Our analyses showed that lungs from DBD donors have upregulation of inflammatory cytokines and pathways. In contrast, DCD lungs display a transcriptome signature of pathways associated with cell death, apoptosis and necrosis. Network centrality revealed specific drug targets to rehabilitate DBD lungs. Moreover, in DBD lungs, tumour necrosis factor receptor-1/2 signalling pathways and macrophage migration inhibitory factor-associated pathways were activated in the EVLP group The examination of gene expression profiling indicates that DBD and DCD lungs have distinguishable biological transcriptome signatures.

Identifiants

DOI: 10.1183/13993003.00327-2020 PMID: 33122335
pubmed: 33122335
pii: 13993003.00327-2020
doi: 10.1183/13993003.00327-2020
pii:
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : CIHR
ID : MOP-31227
Pays : Canada
Organisme : CIHR
ID : MOP-119514
Pays : Canada
Organisme : CIHR
ID : PJT-148847
Pays : Canada

Informations de copyright

Copyright ©ERS 2021.

Déclaration de conflit d'intérêts

Conflict of interest: C. Baciu has nothing to disclose. Conflict of interest: A. Sage has nothing to disclose. Conflict of interest: R. Zamel has nothing to disclose. Conflict of interest: J. Shin has nothing to disclose. Conflict of interest: X-H. Bai has nothing to disclose. Conflict of interest: O. Hough has nothing to disclose. Conflict of interest: M. Bhat has nothing to disclose. Conflict of interest: J.C. Yeung has nothing to disclose. Conflict of interest: M. Cypel has nothing to disclose. Conflict of interest: S. Keshavjee reports grants from Canadian Institutes of Health Research (operating grants MOP-31227, MOP-119514 and PJT-148847) and Genome Canada (Genomic Application Partnership Program grant 6427), during the conduct of the study. Conflict of interest: M. Liu reports grants from Canadian Institutes of Health Research (operating grants MOP-31227, MOP-119514 and PJT-148847) and Genome Canada (Genomic Application Partnership Program grant 6427), during the conduct of the study.

Auteurs

Cristina Baciu (C)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
ORCID: 0000-0002-3750-5147

Andrew Sage (A)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.

Ricardo Zamel (R)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
ORCID: 0000-0002-4802-0022

Jason Shin (J)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.

Xiao-Hui Bai (XH)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.

Olivia Hough (O)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.

Mamatha Bhat (M)

Multiorgan Transplant Program, University Health Network, Toronto, ON, Canada.
Division of Gastroenterology, University of Toronto, Toronto, ON, Canada.

Jonathan C Yeung (JC)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Multiorgan Transplant Program, University Health Network, Toronto, ON, Canada.
Toronto Lung Transplant Program, Dept of Surgery, University of Toronto, Toronto, ON, Canada.

Marcelo Cypel (M)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Multiorgan Transplant Program, University Health Network, Toronto, ON, Canada.
Toronto Lung Transplant Program, Dept of Surgery, University of Toronto, Toronto, ON, Canada.
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Shaf Keshavjee (S)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Multiorgan Transplant Program, University Health Network, Toronto, ON, Canada.
Toronto Lung Transplant Program, Dept of Surgery, University of Toronto, Toronto, ON, Canada.
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
These authors share senior authorship.

Mingyao Liu (M)

Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.
Multiorgan Transplant Program, University Health Network, Toronto, ON, Canada.
Toronto Lung Transplant Program, Dept of Surgery, University of Toronto, Toronto, ON, Canada.
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
These authors share senior authorship.
ORCID: 0000-0002-9188-8417

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Classifications MeSH

questionsmedicales.fr › Procédures de chirurgie opératoire › Circulation extracorporelle › Transcriptomic investigation reveals...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Transcriptomic investigation reveals...
questionsmedicales.fr › Appareil respiratoire › Poumon › Transcriptomic investigation reveals...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation d'organe › Transplantation pulmonaire › Transcriptomic investigation reveals...
questionsmedicales.fr › Techniques d'investigation › Perfusion › Transcriptomic investigation reveals...
questionsmedicales.fr › Personnes › Donneurs de tissus › Transcriptomic investigation reveals...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Transcriptomic investigation reveals...