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Distinct Transcriptional Changes in Donor Kidneys upon Brain Death Induction in Rats: Insights in the Processes of Brain Death
Author(s) -
Schuurs Theo A.,
Gerbens Frans,
Van Der Hoeven Joost A.B.,
Ottens Petra J.,
Kooi Krista A.,
Leuvenink Henri G.D,
Hofstra Robert M.W.,
Ploeg Rutger J.
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00607.x
Subject(s) - medicine , inflammation , gene , signal transduction , gene expression , microarray analysis techniques , biology , immunology , microbiology and biotechnology , genetics
Brain death affects hormone regulation, inflammatory reactivity and hemodynamic stability. In transplant models, donor organs retrieved from brain dead (BD) rats suffer from increased rates of primary non‐function and lower graft survival. To unravel the mechanisms behind brain death we have performed DNA microarray studies with kidney‐derived RNA from normo‐ and hypotensive BD rats, corresponding with optimal and marginal BD donors, respectively. In kidneys from normotensive donors 63 genes were identified as either up‐ (55) or down‐regulated (8), while 90 genes were differentially expressed (67 up‐regulated) in hypotensive BD donor kidneys. Most genes were categorized in different functional groups: metabolism/transport (including the down‐regulated water channel Aqp‐2), inflammation/coagulation (containing the largest number (16) of up‐regulated genes including selectins, Il‐6, α‐ and β‐fibrinogen), cell division/fibrosis (including KIM‐1 involved in tubular regeneration) and defense/repair (with the cytoprotective genes HO‐1, Hsp70, MnSOD2). Also, genes encoding transcription factors (including immediate early genes as Atf‐3, Egr‐1) and proteins involved in signal transduction (Pik3r1) were identified. Summarizing, the use of DNA microarrays has clarified parts of the process of brain death: Brain‐death‐induced effects ultimately lead, via activation of transcription factors and signal transduction cascades, to differential expression of different “effector” genes. Not only deleterious processes such as inflammation and fibrosis occur in brain dead donor kidneys but genes involved in protection and early repair processes are activated as well. These findings can be used to introduce specific cytoprotective interventions in the brain dead donor to better maintain or even increase organ viability.