Gene expression of receptor for advanced glycosylation end products and its modulation by aminoguanidine in diabetic kidney tissue.

OBJECTIVE: To explore the relationship between receptor for advanced glycosylation end products (RAGE) gene expression in the kidneys of diabetic rats and the role of aminoguanidine on it.

METHODS: Among four groups of rats, 2 groups received streptozotocin (STZ) to induce diabetics (DM) and were followed by either aminoguanidine (AG) treatment for 12 weeks or no therapy. Two groups of normal rats in which one received AG and the other given water served as control (Con). Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the amount of receptor of advanced glycosylation and products (RAGE) messenger RNA (mRNA) expression.

RESULTS: After 4 weeks of diabetes inducement, RAGE mRNA levels showed a continuous increase up to 12 weeks both in diabetic renal cortex and medulla compared with mRNA levels at the end of 2 weeks. The RAGE mRNA levels in renal cortex and medulla of control rats did not change significantly with age. AG as the prototype inhibitor of advanced glycosylation end products (AGEs) formation, when administered to diabetic rats for 4 weeks, had no visible effect on the alterations of renal RAGE mRNA in diabetes. By continuous administration up to 8 weeks, those alterations of RAGE mRNA both in diabetic renal cortex and medulla were all ameliorated [P < 0.05, (diabetes without AG) versus (diabetes with AG)]. In addition, diabetic animals had a progressive increase in urinary protein excretion compared to control rats from week 4 onwards. Similarly, after 8 weeks diabetic rats had significantly higher glycated Hb (GHb) (DM without AG vs Con: 7.71 +/- 0.22% vs 2.95 +/- 0.52% P < 0.001). AG treatment for 8 weeks decreased GHb by 24.78% and retarded the rate of rise in albuminuria in diabetic rats as compared with that in untreated diabetic rats (DM with AG vs DM without AG: 22.04 +/- 0.91 micrograms/24 h vs 70.25 +/- 13.05 micrograms/24 h, P < 0.001).

CONCLUSIONS: Gene expression of RAGE in renal cortex and medulla was altered in diabetic rats and excessive gene expression of RAGE in kidney tissue may enhance the interactions between advanced glycosylation end products (AGEs) and its receptor (RAGE) which would contribute to the development of diabetic nephropathy. Cumulative AGEs play an important role in increasing RAGE gene expression in vivo. The decrease of AGEs level by AG therapy ameliorate the abnormal regulation of RAGE gene expression.