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

Area of Science:

• Biochemistry
• Nephrology
• Endocrinology

Background:

• Aberrantly high D-ribose levels are found in type II diabetic patients.
• D-ribose glycates proteins faster than D-glucose, producing advanced glycation end products (AGEs).
• AGE accumulation is linked to impaired renal function, but mechanisms remain unclear.

Purpose of the Study:

• To investigate if D-ribose induces renal dysfunction via the receptor of AGEs (RAGE)-dependent nuclear factor kappa B (NF-κB) signaling pathway.
• To elucidate the molecular mechanisms underlying D-ribose-induced nephropathy.

Main Methods:

• In vivo studies using mice treated with D-ribose.
• In vitro studies using human mesangial cells.
• Immunohistochemistry, western blot, immunofluorescent staining, co-immunoprecipitation, and gene silencing (RAGE).

Main Results:

• D-ribose administration lowered blood glucose and improved insulin tolerance in vivo.
• Mice receiving D-ribose showed increased urine nitrogen and creatinine excretion, severe renal damage, and elevated kidney levels of NF-κB, AGEs, and RAGE.
• In vitro, D-ribose induced NF-κB activation, AGEs, and RAGE accumulation in mesangial cells.
• RAGE silencing blocked D-ribose-induced NF-κB phosphorylation.

Conclusions:

• D-ribose induces inflammation via the RAGE-dependent NF-κB pathway.
• This RAGE-dependent NF-κB activation is a potential triggering mechanism for D-ribose-induced nephropathy in type II diabetes.