DNA aptamer raised against receptor for advanced glycation end products suppresses renal tubular damage and improves insulin resistance in diabetic mice

• Published in: Diabetes & vascular disease research Vol. 18; no. 1; p. 1479164121990533
• Main Authors: Sotokawauchi, Ami, Matsui, Takanori, Higashimoto, Yuichiro, Nishino, Yuri, Koga, Yoshinori, Yagi, Minoru, Yamagishi, Sho-ichi
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2021
• Subjects: Original; tubular injury; Aptamer; AGEs; RAGE; diabetic nephropathy
• ISSN: 1479-1641; 1752-8984
• DOI: 10.1177/1479164121990533

Objective: Interaction of advanced glycation end products (AGEs) with the receptor RAGE plays a role in diabetic nephropathy. However, effects of RAGE-aptamer on tubular damage remain unknown. We examined whether RAGE-aptamer inhibited tubular damage in KKAy/Ta mice, obese type 2 diabetic mice with insulin resistance. Materials and Methods: Male 8-week-old KKAy/Ta mice received continuous intraperitoneal infusion of either control-aptamer or RAGE-aptamer for 8 weeks. Blood biochemistry and blood pressure, and urinary N-acetyl-β-D-glucosaminidase (NAG) activity and albumin excretion levels were monitored. Kidney and adipose tissue samples were obtained for immunohistochemical analyses. Results: Although RAGE-aptamer did not affect blood glucose, blood pressure, body weight, or serum creatinine values, it significantly inhibited the increase in urinary NAG activity and HOMA-IR in diabetic mice at 12 and 16 and at 16 weeks old, respectively. Furthermore, compared with control-aptamer-treated mice, renal carboxymethyllysine, RAGE, and NADPH oxidase-driven superoxide generation were significantly decreased in RAGE-aptamer-treated mice at 12 weeks old with subsequent amelioration of histological alterations in glomerular and interstitial area, while adipose tissue adiponectin expression was increased. Conclusion: Our present results suggest that RAGE-aptamer could inhibit tubular injury in obese type 2 diabetic mice partly by suppressing the AGE-RAGE-oxidative stress axis and improving insulin resistance.