Influence of ischaemia/reperfusion and LFA-1 inhibition on telomere lengths and CDKI genes in ex vivo haemoperfusion of primate kidneys
Corresponding Author
Archil B. Chkhotua
National Centre of Urology, Tsinandali St. 9, 380044 Tbilisi, Georgia
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
E-mail: [email protected] Tel.: +995-99-210021 Fax: +1-507-2620646Search for more papers by this authorHubert Schelzig
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorPeter Wiegand
Department of Legal Medicine, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorStephan Grosse
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorSimone Reis
Department of Legal Medicine, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorMartina Art
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorDietmar Abendroth
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorCorresponding Author
Archil B. Chkhotua
National Centre of Urology, Tsinandali St. 9, 380044 Tbilisi, Georgia
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
E-mail: [email protected] Tel.: +995-99-210021 Fax: +1-507-2620646Search for more papers by this authorHubert Schelzig
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorPeter Wiegand
Department of Legal Medicine, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorStephan Grosse
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorSimone Reis
Department of Legal Medicine, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorMartina Art
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorDietmar Abendroth
Transplantation Centre, University Clinic of Ulm, Ulm, Germany
Search for more papers by this authorA.B. Chkhotua and H. Schelzig share firs authorship
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.
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