EPO Derivative ARA290 Attenuates Early Renal Allograft Injury in Rats by Targeting NF-κB Pathway

Abstract

BackgroundThe goal of this study was to analyze the protective role of ARA290 in early renal allograft injury by using a rat model of renal allograft. MethodsLewis rats were divided into 3 groups: sham, University of Wisconsin solution (UW), and ARA290. A rat model of renal allograft was established by anastomosis using a titanium ring pin stapler. The kidneys were removed 24 hours after transplantation to accomplish the following: (1) examine the protective effect of ARA290 on renal morphology and function; (2) investigate the underlying mechanism by determining the binding affinity of nuclear factor-κB (NF-κB) to DNA by using an electrophoretic mobility shift assay; (3) observe the effect of ARA290 on macrophage infiltration using immunohistochemistry; and (4) detect messenger RNA (mRNA) expression of inflammatory mediators by using reverse transcriptase polymerase chain reaction. ResultsSerum creatinine and blood urea nitrogen levels in the ARA290 group were significantly lower than those in the UW group. Kidney tissue samples from the UW group exhibited morphologic abnormalities and marked macrophage infiltration compared with those in the sham group. In the ARA290 group, renal morphology was greatly improved with decreased macrophage infiltration. The binding affinity of NF-κB to DNA in the ARA290 group was markedly lower than that in the UW and sham groups. The mRNA expression of NF-κB downstream effectors (monocyte chemotactic protein-1; regulated on activation, normal T cell expressed and secreted; intercellular adhesion molecule-1; and vascular cell adhesion molecular-1) was significantly downregulated in the ARA290 group compared with that in the UW group. ConclusionsARA290 protects against early renal allograft injury in rats by reducing macrophage infiltration, improving renal morphology, inhibiting mRNA expression of inflammatory mediators, and weakening the binding affinity of NF-κB to DNA.