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Biomed Res Int. 2018 Aug 16;2018:5717913. doi: 10.1155/2018/5717913. eCollection 2018.

Reperfusion Activates AP-1 and Heat Shock Response in Donor Kidney Parenchyma after Warm Ischemia.

Author information

1
Department of Genetics, Atlas Biomed Group, Moscow, Russia.
2
Moscow Institute of Physics and Technology, Moscow, Russia.
3
Organ Transplant Department, First Pavlov State Medical University, Saint-Petersburg, Russia.
4
Research Centre for Medical Genetics, Moscow, Russia.
5
School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia.
6
Organ Procurement Center, St Petersburg Research Institute for Emergency Named after I.I.Dzanelidze, Saint-Petersburg, Russia.
7
School of Systems Biology, George Mason University, Fairfax, VA, USA.

Abstract

Utilization of kidneys from extended criteria donors leads to an increase in average warm ischemia time (WIT), which is associated with larger degrees of ischemia-reperfusion injury (IRI). Kidney resuscitation by extracorporeal perfusion in situ allows up to 60 minutes of asystole after the circulatory death. Molecular studies of kidney grafts from human donors with critically expanded WIT are warranted. Transcriptomes of two human kidneys from two different donors were profiled after 35-45 minutes of WIT and after 120 minutes of normothermic perfusion and compared. Baseline gene expression patterns in ischemic grafts display substantial intrinsic differences. IRI does not lead to substantial change in overall transcription landscape but activates a highly connected protein network with hubs centered on Jun/Fos/ATF transcription factors and HSP1A/HSPA5 heat shock proteins. This response is regulated by positive feedback. IRI networks are enriched in soluble proteins and biofluids assayable substances, thus, indicating feasibility of the longitudinal, minimally invasive assessment in vivo. Mapping of IRI related molecules in ischemic and reperfused kidneys provides a rationale for possible organ conditioning during machine assisted ex vivo normothermic perfusion. A study of natural diversity of the transcriptional landscapes in presumably normal, transplantation-suitable human organs is warranted.

PMID:
30186861
PMCID:
PMC6116402
DOI:
10.1155/2018/5717913
[Indexed for MEDLINE]
Free PMC Article

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