Influence of ischaemia/reperfusion and LFA-1 inhibition on telomere lengths and CDKI genes in ex vivo haemoperfusion of primate kidneys

Abstract

Abstract The telomere (T) length, p21(WAF1/CIP1) and p27(kip1) cyclin dependent kinase inhibitor (CDKI) genes are the markers of cell senescence and DNA damage. The aim of the study was to determine the influence of renal ischaemia/reperfusion (I/R) and anti-lymphocyte function-associated antigen-1 (LFA-1) monoclonal antibody (mAb) treatment on the value of the above-mentioned markers. Significantly higher levels of p21 and p27 were expressed by the glomeruli (P = 0.001 and P = 0.0001), tubules (P= 0.0065 and P = 0.0006), and interstitial cells (P = 0.0017 and P = 0.0022, respectively) of the xenoperfused kidneys. The mean T length of non-perfused renal specimens (5.56 ±0.60 kbp) was longer than that of the xenoperfused kidneys (5.46 ±0.36 kbp) [P= non-significant (NS)]. Addition of anti LFA-1 mAb did not significantly influence the gene expression profile in the xenoperfused kidneys. The mean T length was longer in the kidneys with anti-LFA-1 mAb than in those without the medication (5.7±0.11 vs 5.13±0.31 kbp) (P= 0.0661). Kidney I/R is associated with telomere shortening and an over-expression of p21 and p27 CDKIs, which indicates substantial DNA damage and/or accelerated tissue senescence. Although anti-LFA-1 mAb had some protective effect on the telomeres, it did not influence the gene expression profile in this study.