Renal ischemia/reperfusion and its influence on telomere length and expression of cell cycle regulatory genes.
The aim of the study was to evaluate the influence of renal ischemia/reperfusion (I/R) on telomere (T) length and tissue expression of cyclin-dependent kinase inhibitor genes (CDKIG). An experimental model of ex-vivo hemoperfusion of the kidney was used as described earlier. Telomere length measurement and expression of p16((INK4a)), p21((WAF1/CIP1)) and p27((Kip1)) CDKIGs was studied immunohistochemically in kidney biopsy samples at baseline and different time points after the reperfusion. The mean T length decreased after reperfusion from 5.56+/-0.60 kbp to 5.46+/-0.36 kbp (p=NS). All 3 genes were up-regulated in kidney tissue however their activation was different in diverse renal cells according to the reperfusion time. Expression of p16 significantly increased in tubular cells at 180 min of reperfusion as compared with the baseline. Activation of the p27 in glomerular cells was significantly higher at 60, 120 and 180 min of reperfusion as compared with 0 and 15 min. The marker started increasing in tubular cells at 15 min and was elevated at every time point afterwards. p21 was significantly over-expressed in all renal cells after the reperfusion. The current study shows that renal I/R causes T shortening and over-expression of CDKIGs indicating on substantial DNA damage and/or accelerated tissue senescence. The tissue expression of CDKIGs is positively related with the reperfusion time.
Chkhotua
A
A
National Centre of Urology, Tbilisi, Georgia.
Abendroth
D
D
Schelzig
H
H
D000818:Animals; D001706:Biopsy; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism; D008251:Macaca; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013552:Swine; D016615:Telomere / Q000648:ultrastructure*
D018797:Cell Cycle Proteins