Thrombospondin-1 mRNA expression in experimental kidney transplantation with heart-beating and non-heart-beating donors.

Background: Ischemia-reperfusion (IR) is a risk factor for delayed graft function, a clinical syndrome more frequently observed in non-heart-beating donors (NHBDs). Previous studies have reported that transforming growth factor-beta1 (TGF-beta1) and hypoxia-inducible factor-1alpha (HIF-1alpha) gene expression increase in the first few days after kidney transplant and that this increase in TGF-beta1 expression is lower in NHBD animals. The purpose of this study was to extend the gene profile analysis by characterizing TGF-beta1 activator thrombospondin-1 (TSP-1) and genes related to HIF-1alpha such as heme oxygenase-1 (HO-1), nitric oxide synthase-2 (NOS-2) and NOS-3.

Methods: The experimental pig model of kidney transplantation comprised heart-beating donors (HBDs, n=9) and NHBDs (n=22). Cortical biopsies were collected after anesthetic induction (baseline), after warm ischemia (WI), after cold ischemia (CI), after 1 hour of reperfusion (1R) and 5 days (5D) after transplant. TSP-1, HO-1, NOS-2 and NOS-3 mRNA expression was determined by real-time PCR.

Results: No change in expression of any of the genes analyzed was found during the transplant procedure (WI, CI, 1R) in HBD and NHBD cortical samples. TSP-1 mRNA was significantly increased at 5D in NHBD animals but unchanged in the HBD group. HO-1 was up-regulated in HBD (p<0.05) and NOS-2 mRNA was significantly increased in both groups (p<0.05). No difference in NOS-3 expression was observed at 5D.

Conclusions: The increased TSP-1 expression in NHBDs may indicate a compensatory response to the reported diminished TGF-beta1 expression. The augmented NOS-2 and HO-1 expression in HBDs could have a positive effect on the recovery of kidney function.