부산대학교 도서관

Recently, aberrantly high levels of D-ribose havebeen discovered in type II diabetic patients. D-ribose glycatesproteins more rapidly than D-glucose, resulting in theproduction of advanced glycation end products (AGEs). Accumulations of these products can be found in impairedrenal function, but the mechanisms are poorly understood. The present study tested whether D-ribose induces renaldysfunction via the RAGE-dependent NF-jB signalingpathway. In vivo, administration of D-ribose was found tolower blood glucose and regulate insulin tolerance. Comparedto controls, urine nitrogen and creatinine excretionwere increased in mice receiving D-ribose and wereaccompanied by severe pathological renal damage. Furthermore,immunohistochemistry showed that NF-jB,AGEs, and receptor of AGEs (RAGE) increased in thekidneys of the mice with D-ribose treatment. In vitro, bywestern blot and immunofluorescent staining, we confirmedthat D-ribose induced NF-jB activation and accumulationof AGEs and RAGE in mesangial cells. By coimmunoprecipitation,we found that the pull-down ofRAGE remarkably increased the expression of NF-jB. Silencing the RAGE gene blocked the phosphorylation ofNF-jB induced by D-ribose. These results strongly suggestthat D-ribose induced NF-jB inflammation in a RAGEdependentmanner, which may be a triggering mechanismleading to nephropathy.