supplementary_table_final_05.24.2021.xlsx (11.27 kB)
Download fileVaccination Against Receptor for Advanced Glycation End Products Attenuates the Progression of Diabetic Kidney Disease
figure
posted on 2021-06-21, 18:24 authored by Tatsuhiko Azegami, Takashin Nakayama, Kaori Hayashi, Akihito Hishikawa, Norifumi Yoshimoto, Ran Nakamichi, Hiroshi ItohEffective
treatment of diabetic kidney disease (DKD) remains a large unmet medical need.
Within the disease’s complicated pathogenic mechanism, activation of the advanced
glycation end-products (AGEs)–receptor for AGEs (RAGE) axis plays a pivotal
role in the development and progression of DKD. To provide a new therapeutic
strategy against DKD progression, we developed a vaccine against RAGE. Three
rounds of immunization of mice with the RAGE vaccine successfully induced
antigen-specific serum IgG antibody titers, and elevated antibody titers were
sustained for at least 38 weeks. In addition, RAGE vaccination significantly
attenuated the increase in urinary albumin excretion in streptozotocin-induced
diabetic mice (type 1 diabetes model) and leptin-receptor–deficient db/db
mice (type 2 diabetes model). In microscopic analyses, RAGE vaccination
suppressed glomerular hypertrophy and mesangial expansion in both diabetic
models and significantly reduced glomerular basement membrane thickness in
streptozotocin-induced diabetic mice. Results of an in vitro study indicated
that the serum IgG antibody elicited by RAGE vaccination suppressed the
expression of AGE-induced vascular cell adhesion molecule 1 and intracellular
adhesion molecule 1 in endothelial cells. Thus, our newly developed RAGE
vaccine attenuated the progression of DKD in mice and is a promising potential
therapeutic strategy for patients with DKD.