1. Academic Validation
  2. D-ribose induces nephropathy through RAGE-dependent NF-κB inflammation

D-ribose induces nephropathy through RAGE-dependent NF-κB inflammation

  • Arch Pharm Res. 2018 Aug;41(8):838-847. doi: 10.1007/s12272-018-1061-z.
Jinni Hong 1 2 Xuemei Wang 1 Ning Zhang 1 Hong Fu 1 Weiwei Li 3
Affiliations

Affiliations

  • 1 Integrated Laboratory of Traditional Chinese Medicine and Western Medicine, Peking University First Hospital, Beijing, 100034, People's Republic of China.
  • 2 Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • 3 Integrated Laboratory of Traditional Chinese Medicine and Western Medicine, Peking University First Hospital, Beijing, 100034, People's Republic of China. weiwei_ivy@163.com.
Abstract

Recently, aberrantly high levels of D-ribose have been discovered in type II diabetic patients. D-ribose glycates proteins more rapidly than D-glucose, resulting in the production of advanced glycation end products (AGEs). Accumulations of these products can be found in impaired renal function, but the mechanisms are poorly understood. The present study tested whether D-ribose induces renal dysfunction via the RAGE-dependent NF-κB signaling pathway. In vivo, administration of D-ribose was found to lower blood glucose and regulate Insulin tolerance. Compared to controls, urine nitrogen and creatinine excretion were increased in mice receiving D-ribose and were accompanied by severe pathological renal damage. Furthermore, immunohistochemistry showed that NF-κB, AGEs, and receptor of AGEs (RAGE) increased in the kidneys of the mice with D-ribose treatment. In vitro, by western blot and immunofluorescent staining, we confirmed that D-ribose induced NF-κB activation and accumulation of AGEs and RAGE in mesangial cells. By co-immunoprecipitation, we found that the pull-down of RAGE remarkably increased the expression of NF-κB. Silencing the RAGE gene blocked the phosphorylation of NF-κB induced by D-ribose. These results strongly suggest that D-ribose induced NF-κB inflammation in a RAGE-dependent manner, which may be a triggering mechanism leading to nephropathy.

Keywords

AGEs; Diabetes; Kidney; RAGE.

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