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 gl ycosylation end products (RAGE) gene expression in the kidneys of diab etic rats and the role of aminoguanidine on it. Methods Among four gro ups of rats, 2 groups received streptozotocin (STZ) to induce diabetic s (DM) and were followed by either aminoguanidine (AG) treatment for 1 2 weeks or no therapy. Two groups of normal rats in which one received AG and the other given water served as control (Con). Reverse transcr iption-polymerase chain reaction (RT-PCR) was used to measure the amou nt 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 d iabetic renal cortex and medulla compared with mRNA levels at the end of 2 weeks. The RAGE mRNA levels in renal cortex and medulla of contro l rats did not change significantly with age. AG as the prototype inhi bitor of advanced glycosylation end products (AGEs) formation, when ad ministered to diabetic rats for 4 weeks, had no visible effect on the alterations of renal RAGE mRNA in diabetes. By continuous administrati on up to 8 weeks, those alterations of RAGE mRNA both in diabetic rena l cortex and medulla were all ameliorated [P < 0.05, (diabetes without AG) versus (diabetes with AG)I. In addition, diabetic animals had a p rogressive increase in urinary protein excretion compared to control r ats from week 4 onwards. Similarly, after 8 weeks diabetic rats had si gnificantly higher glycated Hb (GHb) (DM without AG vs Con: 7.71+/-0.2 2% 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 ra ts as compared with that in untreated diabetic rats (DM with AG vs DM without AG: 22.04 +/- 0.91 mu g/24h vs 70.25 +/- 13.05 mu g/24h, 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 glycosyla tion end products (AGEs) and its receptor (RAGE) which would contribut e to the development of diabetic nephropathy. Cumulative AGEs play an important role in increasing RAGE gene expression in vivo. The decreas e of AGEs level by AG therapy ameliorate the abnormal regulation of RA GE gene expression.