Ischemic Epigenetics and the Transplanted Kidney

摘要: The primary purpose of this investigation was to study oxidative demethylation DNA following ischemia/reperfusion injury (I/RI) that putatively influences posttransplant gene expression in transplanted kidneys. Our hypothesis as a result I/RI, damage, which is inherent solid organ transplantation, may lead aberrant cytosine-guanine (CpG) sites within promoter regions DNA. methylated CpG normally contribute the binding proteins render inaccessible transcription factors. Therefore, conversion cytosines nonmethylated by damage postischemic organs might facilitate enhanced donor exposing demethylated site DNA-binding enhance transcription. In study, we investigated specific IFNgamma response element resident region C3 rat kidney. 24 hours cold ischemia and subsequent 2 reperfusion an isolated ex-vivo circuit, observed significant change ratio unmethylated at site. Epigenetic modifications have not been previously investigated, but our own data suggests they potential modify posttransplantation. Since epigenetic modification become stable heritable upon mitosis, such changes persist with enormous implications for transplant outcomes.