Effect of ischemia/reperfusion on telomere length and CDKI genes expression in a concordant ex-vivo hemoperfusion model of primate kidneys.
OBJECTIVE
The telomere (T) length, p21(WAF1/CIP1) and p27(Kip1) cyclin dependent kinase inhibitor (CDKI) genes are considered the markers of cell senescence and DNA damage. The aim of the study was to evaluate the influence of renal ischemia/reperfusion (I/R) on the value of above-mentioned markers.


METHODS
13 Macaque cynomolgus monkey kidneys were harvested and placed in Eurocollins solution. 9 kidneys were ex-vivo perfused with human blood and 4 kidneys were not perfused at all (control group). Tissue expression of p21(WAF1/CIP1) and p27(Kip1) was evaluated immunohistochemically and the T lengths were measured by southern blotting technique.


RESULTS
Significantly higher levels of p21 and p27 were expressed by the glomeruli (p = 0.001 and 0.0001), tubules (p = 0.0065 and 0.0006) and interstitial cells (p = 0.0017 and 0.0022, respectively) of the xenoperfused kidneys. The mean T length was higher in the control group (5.56 +/- 0.60 kbp) than in the study group kidneys (5.46 +/- 0.36 kbp) (P = NS).


CONCLUSIONS
Renal I/R is associated with telomere shortening and an over-expression of p21 and p27 genes indicating substantial DNA damage and/or accelerated tissue senescence.
Schelzig
Hubert
H
Transplantation Centre, University Clinic Ulm, Ulm, Germany. hubert.schelzig@medizin.uni-ulm.de
Chkhotua
Archil B
AB
Wiegand
Peter
P
Grosse
Stephan
S
Reis
Simone
S
Art
Martina
M
Abendroth
Dietmar
D
D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics*; D005786:Gene Expression Regulation; D006464:Hemoperfusion; D007511:Ischemia; D007668:Kidney / Q000098:blood supply* / Q000166:cytology / Q000502:physiology*; D007678:Kidney Glomerulus / Q000166:cytology; D008252:Macaca fascicularis; D023421:Models, Animal; D009926:Organ Preservation; D015424:Reperfusion; D016615:Telomere / Q000648:ultrastructure*
D016203:CDC2 Protein Kinase