Epidermal growth factor was shown to increase SCF expression further. These Ginsenoside-Ro findings may provide a mechanism for the sharp increase in SCF expression at day 1 after ischemia. Further studies should demonstrate whether HIF-1a and EGF are the driving force behind activation of SCF expression in the proximal tubules during I/R injury. Local down-regulation of SCF in the corticomedullary area did not affect granulocyte influx following ischemia when compared to control animals. As tubular injury, tubular epithelial proliferation and apoptosis were affected by ASON-treatment, we investigated the role of SCF/c-KIT signaling using an in vitro model for hypoxia. In line with this, we found a role for SCF in cell survival following in vitro hypoxic injury. Furthermore, we could establish that SCF induces phosphorylation of c-KIT and Bad, suggesting that this pathway is involved the survival of cells following in vitro hypoxia. Using kidney lysates from NSON and ASON-treated animals, we found that c-KIT phosphorylation was virtually absent after ischemia in ASON-treated animals but not in the NSON-treated controls. This was reflected by increased phosphorylation of Akt in control animals after ischemia which was lower in ASON-treated animals. Several SCF knockout animals have been described whereby most homozygote SCF mutations are lethal due to severe anemia. Mice that are compound heterozygotes for the SCF alleles KitlSl/KitlSl-d are viable, but display severe defects such as macrocytic anemia but also renal malformations. These include thickening of the glomerular basement membrane, increased glomerular cellularity but also increased mesangial matrix deposition and severe malformations of the distal nephrons. This phenotype does not permit the use of these animals in experimental renal I/R injury. We have therefore applied a different strategy to block SCF expression by preventing mRNA translation using ASON treatment. This approach has several important benefits over other approaches. First, expression is only transiently reduced and bypasses the occurrence of adaptive mechanism that may be observed in knockout animals as result of the specific genetic deletion. Second, phosphorothioate capped oligonucleotides are distributed to the kidney, more specifically to the glomerular parietal and the tubular epithelium in the corticomedullary area and has been used in previous studies with success. The fact that we found no differences between vehicle and NSON treated animals with respect to tubular injury or renal function following I/R injury indicates that the oligonucleotides do not affect TEC by inducing renoprotection or, the opposite, being cytotoxic. Unfortunately we are unable to demonstrate the effect of ASON on translation of target genes in vitro. We speculate that upon in vitro cell culture, the proximal TEC lose their capacity to properly engage in reabsorption or uptake processes as a result of imperfect polarization, thus limiting the uptake of oligonucleotides. However, addition of SCF to hypoxic cells in vitro does supplement and support our in vivo findings by decreasing the rate of apoptosis in cultured IM-PTEC cells whereas a decrease of SCF expression by ASON treatment increases apoptosis of TEC in vivo. Here we have shown that c-KIT and SCF expression occurs in tubules in the corticomedullary area during I/R injury. Reduced expression of SCF leads to increased TEC apoptosis. Catharanthine sulfate Hypoxia has been shown to regulate SCF expression in vitro and addition of SCF reduces caspase 3-mediated apoptosis via phosphorylation of Bad. This protective interaction appears to be an autocrine mode of TEC survival following I/R injury. Whether SCF and c-KIT also mediate other protective adaptations to hypoxic injury in vivo and in vitro has to be determined in future studies. While our knowledge of how plants perceive pathogens and activate associated defense signaling pathways is increasing rapidly, less is known about how these processes are regulated during the infection. A predominant theme that is emerging is that of ubiquitination as a means of targeting the plant immune.